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 .
Priority
The instant application claims priority to provisional application 63/472,968, filed on 06/14/2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/15/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because of the following informalities: Spelling/typographical error. Specification page 5 line 8 contains the term “PK-ß agonist”. The term should be corrected to read “PKC-ß agonist”. Appropriate correction is required.
Claim Rejections - 35 USC § 112 – Second Paragraph
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 1-4, 8, and 12-17 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.
Claim 1 is indefinite for reciting the phrase “wherein the pharmaceutical composition is formulated for local delivery to a gingival tissue”, because a person of ordinary skill in the art would not reasonable be able to understand the metes and bounds of the claim. The indicated recitation makes it unclear as to what form the composition takes, as local delivery to gingival tissue could encompass a number of possible forms (i.e., pills, tablets, topical gels, etc.) not indicated in the claim.
Claim 2 is indefinite for reciting the phrase “pharmaceutically acceptable derivative”, because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. In the chemical art, the term “derivative” is generally understood to mean a compound having a distinct structure which shares a base or “backbone” structure with a parent compound. It is unclear from both the disclosure and recitation of the claim what a “derivative” of gnidimacrin encompasses because any chemical alteration to the structure of gnidimacrin may fall within such a wide breadth.
Claim 3 is indefinite for reciting the phrase “wherein the therapeutically effective amount of the PKC-β agonist is sufficient to achieve a concentration of up to about 100 nM gnidimacrin in the gingival tissue of the subject”, because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. It is unclear what amount would be needed to achieve the target concentration in the gingival tissue; the reason being that such an amount could be dependent upon multiple absent variables such as route of administration, dosing method, form of the dosing composition, weight of the subject, etc. Furthermore, the recited amount is tied to the administering of the composition to a subject, which is outside of the scope of the composition itself.
Claim 4 is indefinite for reciting the phrase “wherein the pathogen comprises a bacterium and the bacterium is Porphyromonas gingivalis”, because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. Claim 1 is directed to a composition of matter. While the preamble of claim 1 may indicate an intended use or purpose of said composition, such an intended use or purpose cannot be considered as limiting or contributing to the structure of the composition. As the instant claim seeks to further limit the non-limiting preamble of claim 1, the instant claim is indefinite. See MPEP 2111.02(II):
If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020) (The court found that the preamble in one patent’s claim is limiting but is not in a related patent); Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) ("where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation")
Claim 8 is indefinite for reciting the term “periodontitis-related condition”, because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. Under broadest reasonable interpretation, the term “condition” may encompass individual diseases and disorders distinct from the target periodontitis, and it is unclear what possible conditions are being claimed.
Claim 8 is indefinite for reciting the phrase “wherein the pharmaceutical composition is formulated for local delivery to a gingival tissue”, because a person of ordinary skill in the art would not reasonable be able to understand the metes and bounds of the claim. The indicated recitation makes it unclear as to what form the composition takes, as local delivery to gingival tissue could encompass a number of possible forms (i.e., pills, tablets, topical gels, etc.) not indicated in the claim.
Claim 9 is indefinite for reciting the phrase “wherein the therapeutically effective amount of the gnidimacrin or the pharmaceutical derivative thereof is sufficient to achieve a concentration of about 10 nM to about 100 nM gnidimacrin or pharmaceutical derivative thereof in the gingival tissue of the subject”, because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. It is unclear what amount would be needed to achieve the target concentration in the gingival tissue; the reason being that such an amount could be dependent upon multiple absent variables such as route of administration, dosing method, form of the dosing composition, weight of the subject, etc. Furthermore, the recited amount is tied to the administering of the composition to a subject, which is outside of the scope of the composition itself.
Claim 12 is indefinite for reciting the term “periodontitis-related condition”, because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. Under broadest reasonable interpretation, the term “condition” may encompass individual diseases and disorders distinct from the target periodontitis, and it is unclear what possible conditions are being claimed.
Claim 13 is indefinite for reciting the term “periodontitis-related condition”, because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. The instant claim is indefinite for the same reasons as parent claim 12.
Claim 14 is indefinite for reciting the phrase “the compound”, because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. Parent claims 12 and 1 do not recite a “compound”. Accordingly, the instant claim provides improper antecedence.
Claim 15 is indefinite for reciting the phrase “the compound”, because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. Parent claims 12 and 1 do not recite a “compound”. Accordingly, the instant claim provides improper antecedence.
Claim 16 is indefinite for reciting the term “PK-ß agonist”, because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. Both the claims and the specification of the instant application appear to be drawn towards “PKC-ß” agonists. As “PK-ß agonist” does not appear to be defined in either the instant claims or the specification, the claim is indefinite. If the recitation is the result of a spelling or typographical error, then this rejection may be overcome by amending the term to “PKC-ß” agonist.
Claim 16 is indefinite for reciting the phrase “an effective concentration of PK-B agonist” (underlined for emphasis), because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. The use of the term “concentration” makes the claim unclear because it cannot be determined whether the desired effect of the administration is based upon the concentration of a composition comprising the target active compound or the amount of target compound administered. Furthermore, the use of the term “concentration” indicates that the actual amount of active administered could vary based upon an unspecified dosing volume. It is recommended to amend the instant claim such that the term “concentration” is altered to “amount”.
Claim 17 is indefinite for reciting the phrase “an effective concentration of PK-B agonist” (underlined for emphasis), because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. The instant claim is indefinite for the same reasons as claim 16 above with regards to the recitation of the term “concentration”. It is recommended to amend the instant claim such that the term “concentration” is altered to “amount”.
Claim Rejections - 35 USC § 112 – First Paragraph
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, 12, and 16 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 inclusion of gnidimacrin and pharmaceutically acceptable salts, does not reasonably provide enablement for any and all PKC-ß agonists. 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 use of the invention commensurate in scope with these claims.
Claim 1 recites a pharmaceutical composition comprising a PKC-ß agonist, claim 12 recites a method of treating periodontitis by administering a composition of claim 1, and claim 16 recites a method of reducing the likelihood of invasion of a host cell by an intracellular bacterium by contacting said host cell with an effective concentration of PKC-ß agonist.
Looking towards Applicant’s specification for guidance, working examples are provided on pages 29-34 which describe assays carried out to assess the ability of gnidimacrin to inhibit invasion of human oral keratinocytes by p.gingivalis. Specification pages 32-33 further indicate that said assays were only tested with gnidimacrin and p.gingivalis. Accordingly, while such exemplary findings would be enabling for the use of gnidimacrin on p.gingivalis, such findings cannot reasonably be extrapolated to any and all PKC-ß agonists, or (in the case of claim 16) invasion by any intracellular bacterium due to potential material differences between potential PKC-B agonists, and biological differences between species of bacteria. Furthermore, the disclosure has not provided any indication that gnidimacrin would have wide spectrum antibacterial properties. Accordingly, the claims at hand provide a scope which far outpaces what has been demonstrably set forth in the disclosure.
Additionally, claims dependent upon claims 1, 12, and 16 would also be rejected for the same reasons. While dependent claims 2, 15, and 18 narrow the PKC-B inhibitor, to “gnidimacrin or a pharmaceutically acceptable derivative”, such derivatives would also be outside the scope of enablement as chemical “derivatives” are considered to be materially distinct from their parent or lead compounds.
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.
(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.
Claim(s) 1-2 and 6-7 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lee (WO 2020/257622 A1).
Claim 1 recites a pharmaceutical composition for inhibiting invasion of a pathogen into a host cell, comprising: a therapeutically effective amount of a protein kinase C beta (PKC-B) agonist and a pharmaceutically acceptable carrier, wherein the pharmaceutical composition is formulated for local delivery to a gingival tissue in a subject.
Lee teaches compounds as gnidimacrin derivatives, compositions comprising such compounds, and methods of use in treating HIV-1 (specification page 4, lines 29-33)1. The teachings of Lee indicate that their disclosed compounds fall within the genus of the following Formula (I) (page 9):
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Formula (I) of Lee is further indicated as a gnidimacrin derivative, which would be considered as a PKC-B agonist. Furthermore, Lee indicates the use of pharmaceutically acceptable carriers in composition (page 22 lines 31-34, page 23 line 1)2. As the teachings of Lee provide a composition comprising a PKC-B agonist and pharmaceutically acceptable carrier, Lee anticipates the instant claim.
Claim 2 further limits the composition of claim 1 wherein the PKC-B agonist comprises gnidimacrin or a pharmaceutically acceptable derivative thereof.
As discussed in the rejection of claim 1, Lee teaches compositions comprising gnidimacrin derivatives having chemical structure of Formula (I).
Claim 6 further limits the composition of claim 1 wherein the composition is formulated as a dentifrice.
Lee teaches that their compositions may be formulated at least as an oral gel (specification page 22 lines 31-34)3, which may be considered as a dentifrice.
Claim 7 further limits the composition of claim 6 wherein the dentifrice comprises a paste, a gel, a mouthwash, a powder, a tooth soap, or a combination thereof.
As discussed in the rejection of claim 6, Lee teaches that their composition may be formulated as an oral gel.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 5, 8, and 10-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lee in view of Dinman (US 2011/0183892 A1).
Claim 5 further limits the composition of claim 1 wherein the composition further comprises a therapeutically effective amount of an antibiotic.
As discussed in the rejection of claim 1, Lee anticipates a composition comprising a PKC-B agonist and a pharmaceutically acceptable carrier. Lee does not explicitly teach the inclusion of an antibiotic. However, it would have been obvious to include an antibiotic because Dinman teaches the use of such antibiotics for the treatment of HIV, and there would have been a reasonable expectation that the inclusion of such components would be successful in treating HIV.
The teachings of Dinman are directed towards the treatment of viral infections by administering aminoglycoside antibiotics. Dinman indicates that aminoglycoside antibiotics are capable of inducing increased amounts of productive programmed ribosomal frameshifting (PRF) events, thereby interfering with viral particle assembly (specification [0004])4. In particular, Dinman indicates an example wherein the administration of gentamicin was able to increase the productive PRF rate in HeLa and Jurkat cells by 40% (specification [0005]). The following figure provides a visual representation of increased PRF events in HIV infected cells (Fig. 2B):
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It would have been prima facie obvious for a person of ordinary skill in the art to arrive at the claimed composition comprising PKC-B agonist and antibiotic, because Lee teaches that gnidimacrin and derivatives thereof are useful for treatment of HIV, while Dinman teaches that gentamicin is useful for the same purpose. There would have been reasonable expectation that the combination of both would have provided synergistic effect in the treatment of at least HIV.
Claim 8 recites a composition comprising a therapeutically effective amount of gnidimacrin or a pharmaceutical derivative thereof; a therapeutically effective amount of an antibiotic; and a pharmaceutically acceptable carrier.
As iterated in the 102 rejection of claim 1, Lee teaches a composition comprising gnidimacrin derivatives and a pharmaceutically effective carrier, and methods of use of said compounds and compositions for the treatment of HIV. Lee does not explicitly teach the inclusion of an antibiotic. However, it would have been obvious to include an antibiotic because Dinman teaches the use of such antibiotics for the treatment of HIV, and there would have been a reasonable expectation that the inclusion of such components would be successful in treating HIV.
The teachings of Dinman are directed towards the treatment of viral infections by administering aminoglycoside antibiotics. Dinman indicates that aminoglycoside antibiotics are capable of inducing increased amounts of productive programmed ribosomal frameshifting (PRF) events, thereby interfering with viral particle assembly (specification [0004])5. In particular, Dinman indicates an example wherein the administration of gentamicin was able to increase the productive PRF rate in HeLa and Jurkat cells by 40% (specification [0005]). The following figure provides a visual representation of increased PRF events in HIV infected cells (Fig. 2B):
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It would have been prima facie obvious for a person of ordinary skill in the art to arrive at the claimed composition comprising PKC-B agonist and antibiotic, because Lee teaches that gnidimacrin and derivatives thereof are useful for treatment of HIV, while Dinman teaches that gentamicin is useful for the same purpose. There would have been reasonable expectation that the combination of both would have provided synergistic effect in the treatment of at least HIV.
Claim 10 further limits the composition of claim 8 wherein the antibiotic comprises gentamicin, metronidazole, or a combination thereof.
Dinman teaches the inclusion of gentamicin.
Claim 11 further limits the composition of claim 8 wherein the gnidimacrin or the pharmaceutical derivative thereof is formulated in a dentifrice and the dentifrice comprises a paste, a gel, a mouthwash, a powder, a tooth soap, or a combination thereof.
Lee teaches that their compositions may be formulated at least as an oral gel (specification page 22 lines 31-34), which may be considered as a dentifrice.
Allowable Subject Matter
While none of the claims at hand are in condition for allowance, the claims are indicated as containing allowable subject matter. More specifically, in regards to aspects of claims 12 and 16. While PKC-B agonists such a gnidimacrin are generally well known in the art and have established use as antiviral agents (such as in use against HIV/AIDS), the prior art does not appear to teach or suggest methods of use of gnidimacrin and compositions thereof for the treatment of periodontitis or as an antibacterial agent against p.gingivalis.
Conclusion
Claims 1-20 are rejected.
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/ERIC TRAN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 “In even yet other aspects, the presently disclosed subject matter provides a method for treating an human immunodeficiency virus (HIV-1) infection in a subject in need of treatment thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or a pharmaceutical composition thereof.”
2 “The compounds can be formulated readily using pharmaceutically acceptable carriers well known in the art into dosages suitable for oral administration. Such earners enable the compounds of the disclosure to be formulated as tablets, pills, capsules, liquids, gels, syrups, slurries, suspensions and the like, for oral ingestion by a subject (e.g., patient) to be treated.”
3 “The compounds can be formulated readily using pharmaceutically acceptable carriers well known in the art into dosages suitable for oral administration. Such earners enable the compounds of the disclosure to be formulated as tablets, pills, capsules, liquids, gels, syrups, slurries, suspensions and the like, for oral ingestion by a subject (e.g., patient) to be treated.”
4 “Stabilizing near cognate interactions is believed to inhibit rejection by the normal proofreading activity of the ribosome and thus, increase the frequency of productive PRF events which, in turn, alters the ratio of viral proteins and results in a collapse of viral particle assembly. PRF is thus considered a promising target for antiviral therapy”
5 “Stabilizing near cognate interactions is believed to inhibit rejection by the normal proofreading activity of the ribosome and thus, increase the frequency of productive PRF events which, in turn, alters the ratio of viral proteins and results in a collapse of viral particle assembly. PRF is thus considered a promising target for antiviral therapy”
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