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 .
Priority
The present application, filed September 15, 2023, is a national stage application of PCT/EP2022/056801, filed March 16, 2022, which claims priority to foreign priority application SE2150302-4, filed Mach 17, 2021.
Status of the Application
Applicant’s communication, received September 15, 2023, wherein claims 2-5 and 15 are canceled and new claims 19-22 are added, is acknowledged.
Claims 1, 6-14, and 16-22 are pending and examined on the merits herein.
Claim Interpretation
Claim 1 recites: A hydrogel comprising chitosan for use in the treatment and/or prevention of an oral inflammatory condition and/or an oral infection and/or for use in endodontic treatment, wherein said hydrogel has a pH of from about 2.5 to about 5.2.
Claims 6-14 and 16-22 depend from claim 1 and further limit the hydrogel of claim 1 or claims methods or kits that require the hydrogel of claim 1.
The limitation “for use in the treatment and/or prevention of an oral inflammatory condition and/or an oral infection and/or for use in endodontic treatment” is interpreted as an intended use of the hydrogel of claim 1.
MPEP 2111.02 (at II) states: “During examination, statements in the preamble reciting the purpose or intended use of the claimed invention must be evaluated to determine whether or not the recited purpose or intended use results in a structural difference (or, in the case of process claims, manipulative difference) between the claimed invention and the prior art. If so, the recitation serves to limit the claim. …To satisfy an intended use limitation which is limiting, a prior art structure which is capable of performing the intended use as recited in the preamble meets the claim.”
In this instance, the limitation “for use in the treatment and/or prevention of an oral inflammatory condition and/or an oral infection and/or for use in endodontic treatment” is interpreted as intended use of the hydrogel of claim 1, and therefore claim 1 is considered satisfied by a hydrogel product that satisfies the limitations of claim 1, even if that hydrogel is not used in the treatment and/or prevention of an oral inflammatory condition and/or an oral infection and/or for use in endodontic treatment.
Claim 10 depends from claim 1 and recites “wherein said hydrogel does not comprise any additional antimicrobial agent, such as an antibiotic, and/or a cross-linking agent.” The broadest reasonable interpretation of claim 10 is that the hydrogel does not contain both an additional antimicrobial agent and a cross-linking agent. Therefore, claim 10 may be satisfied by a hydrogel that satisfies claim 1 and contains either an additional antimicrobial agent or a cross-linking agent, but not both.
Claim Objections
Claim 17 is objected to because of the following informalities:
Claim 17 recites: “A kit comprising d) a brush comprising bristles comprising chitosan as defined in claim 14; and e) a hydrogel as defined in claim 1.” To promote clarity in the claims, the examiner suggests amending claim 17 such that the brush and hydrogel are items a) and b) or 1) and 2) in the list, because beginning a list with d) is unconventional.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
As described in the above claim interpretation section, the examiner is interpreting the present claims as if the intended use of the composition does not limit the structure of the claim. However, for the sake of argument, if this intended use did limit the structure of the claim,
then claims 1, 6-14, and 17-22 would lack enablement for prevention of an oral inflammatory condition and/or an oral infection, as described below.
In addition, claim 16 lacks enablement for preventing an oral inflammatory condition and/or an oral infection, as described below.
Claims 1, 6-14, and 16-22 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 a hydrogel comprising chitosan for use in the treatment of an oral inflammatory condition and/or an oral infection and/or for use in endodontic treatment and for a method of treating an oral inflammatory condition and/or an oral infection and for use in endodontic treatment, does not reasonably provide enablement for a hydrogel comprising chitosan for use in the prevention of an oral inflammatory condition and/or an oral infection and for a method of preventing an oral inflammatory condition and/or an oral infection.
The Applicant’s attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth 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 nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
Nature of the invention: The invention is drawn to a hydrogel for use in the treatment and/or prevention of an oral inflammatory condition and/or an oral infection and/or for use in endodontic treatment, and to a method for treating and/or preventing an oral inflammatory
condition and/or an oral infection and/or for use in endodontic treatment, said method comprising applying a hydrogel comprising chitosan as defined in claim 1 to an oral surface.
With respect to the definition of “prevention”, the claims are given their broadest reasonable interpretation.
The Oxford English Dictionary defines the verb “to prevent” as “to preclude the occurrence of (an anticipated event, state, etc.); to render (an intended, possible, or likely action or event) impractical or impossible by anticipatory action; to put a stop to” (p. 8, definition II.9.a of “prevent”; cited in PTO-892). “Preventing” as recited in the instant application is thus interpreted to mean the complete and total blocking of all oral inflammatory conditions and oral infections for an indefinite period of time. Merely making oral inflammatory conditions and oral infections less likely or less severe would not render the disease impossible and thus not qualify as preventing.
The state of the prior art: The state of the art does not provide an expectation that oral inflammatory conditions and oral infections may be rendered impossible by the hydrogel of claim 1.
As one example of an oral inflammatory condition, Santarelli (Santarelli, A.; et al. International Journal of Immunopathology and Pharmacology 2015, vol. 28, pp. 562-568; cited in PTO-892) teaches that lichen planus is a chronic inflammatory autoimmune disorder mediated by T lymphocytes that involves the stratified squamous epithelial tissue, and that the oral mucosa is commonly affected with a variety of clinical presentations referred to as oral lichen planus. Therefore, oral lichen planus is reasonably considered as an oral inflammatory condition.
Mayo Clinic (Mayo Clinic, website entry for Oral lichen planus; website from December 15, 2019 accessed via the Wayback Machine; cited in PTO-892) teaches that oral lichen planus is a chronic condition, and because there is no cure, the treatment focuses on helping severe lesions heal and reducing pain or other discomfort (p. 2, Treatment section, lines 1-3). Because Mayo Clinic teaches as oral lichen planus as a chronic condition, preventing such a condition would have been unpredictable in view of the prior art discussed here.
Regarding oral infections, Dahlen (Dahlen, G; et al. Journal of Clinical Medicine 2019, vol. 8, 1339; cited in PTO-892) teaches that periodontal diseases affect the supporting tissues of teeth, and the most common, gingivitis and periodontitis, are inflammatory diseases that are induced and maintained by the polymicrobial biofilm that are formed on teeth in the absence of daily oral hygiene procedures (p. 1, Section 1, lines 1-3). Dahlen further teaches that periodontitis is the result of a complex interplay between microorganisms of the dental biofilm
and the host, and that the role of specific microorganisms and their products in the disease initiation and propagation is unclear (p. 1, Section 1, second paragraph, lines 1-3). Dahlen teaches that the severity of the periodontal disease also depends on environmental and host risk factors (p. 1, Section 1, second paragraph, lines 3-4).
Dahlen further teaches that the human oral microbiome is distinctly different from that of other body compartments, comprises a highly diverse microbial population involving more than 700 species. Dahlen teaches that, within the oral microbiome, the dental biofilm has
its own microbiome characterized by strong tooth surface adhering streptococci and actinomyces. Dahlen teaches that adhesion is essential for colonization within the oral cavity and is regulated primarily by the host and host receptors on the mucosal surface and teeth. Dahlen teaches that the host selectively, very early after birth, allows the microorganisms that best fit to the receptors of each individual and the specific environment of the oral cavity to colonize (p. 6, Section 5, lines 1-9). Therefore, one of ordinary skill in the art would have recognized the human oral microbiome as complex, differing between individuals, and would have recognized its essential need for promoting oral health. Accordingly, one of ordinary skill in the art would not have reasonably considered that administration of an antibacterial gel may render all oral infections impossible, because the oral cavity is already colonized with bacteria that are essential for oral health.
Moreover, prevention of a disease of a disease or disorder is not the same as treatment of said disease or disorder. In order to prevent a disease, as opposed to merely delaying or reducing symptoms, a method must either render the subject completely resistant to said disease after a limited number of treatments, or, when continued indefinitely, continue to suppress the occurrence of that disease. The prior art does not provide an expectation that the administration of the presently claimed compounds will render oral inflammatory conditions or oral infections in a subject impossible by anticipatory action.
The relative skill of those in the art: The relative skill of those in the art is high.
The predictability or unpredictability of the art: The lack of prior art disclosing the prevention of all oral inflammatory conditions and oral infections means that one skilled in the art cannot predict the usefulness of a product or method to make these conditions possible.
As described above, one example of an oral inflammatory condition is oral lichen planus, which is a chronic condition with no cure, with treatments intended to help severe lesions heal and reduce pain or other discomfort. The prior art does not provide an expectation that oral lichen planus may be prevented by administering the hydrogel of claim 1 to an oral surface. Similarly, the prior art does not provide an expectation that all oral infections, such as those that arise from the oral microbiome, may be prevented by administering the hydrogel of claim 1 to an oral surface.
Therefore prevention of all oral inflammatory conditions and oral infections using the hydrogel of claim 1 is unpredictable.
The breadth of the claims: The scope of the claims includes a hydrogel comprising chitosan for use in the treatment and/or prevention of an oral inflammatory condition and/or an oral infection and/or for use in endodontic treatment, as well as a method for treating and/or preventing an oral inflammatory condition and/or an oral infection and/or for use in endodontic treatment by applying a hydrogel comprising chitosan as defined in claim 1 to an oral surface. Preventing is interpreted as described in the above Nature of the Invention section.
The amount of direction or guidance presented: The specification provides that in patients with implants, a periodontitis-like condition may develop into a condition called peri-implantitis and is caused by the colonization of bacteria on the implants' surface, and that no predictable treatment strategy has been developed for healing of peri-implantitis (p. 2, lines 7-12).
Moreover, the specification provides that periodontal disease, the most common of which are gingivitis and periodontitis, is caused by bacteria in dental plaque, which is a film constantly forming on the surfaces of the teeth. The specification provides that endodontic infections may if left untreated lead to spread of bacteria from the root canal to the surrounding bone and soft tissues, and thus there is a need to develop antimicrobial agents to increase the outcome of root canal therapy (p. 4, lines 6-14).
The specification does not provide guidance specifically regarding preventing oral inflammatory conditions or oral infections in a subject by applying the hydrogel of claim 1 to an oral surface.
The presence or absence of working examples: The specification provides a working example demonstrating the preparation of chitosan hydrogels (p. 17, Example 1, lines 5-20), instructions for debridement of dental implants with a chitosan brush and a chitosan hydrogel (pp. 19-22, Example 3), and provides a working example for cleaning titanium coins using a chitosan gel and/or chitosan brush (pp. 22-26, Example 4).
Specifically, the specification provides that when a chitosan gel at pH 3.86 is used to decontaminate the titanium coins contaminated with P. gingivalis, no growth of bacteria is observed in connection with the gel and some bacteria are observed in the peripheral area of the gel (pp. 24-25, Examples 3 and 7).
The specification does not provide working examples showing prevention of an oral inflammatory conditions or prevention of oral infections by administration of the presently claimed hydrogel.
Note that a lack of working examples is a critical factor to be considered, especially in a case involving an unpredictable and undeveloped art such as the prevention of oral inflammatory conditions and oral infections. See MPEP 2164.
The quantity of experimentation required: In order to practice the invention of preventing an oral inflammatory condition and/or an oral infection comprising applying a hydrogel comprising chitosan as defined in claim 1 to an oral surface, one of ordinary skill in the art would be required to undertake a novel and extensive research program to show that administration of the hydrogel of claim 1 may render oral inflammatory conditions and oral infections impossible. Because this research would need to be exhaustive, because it would involve a wide scope of oral inflammatory conditions and oral infections for which there is no single cause or mechanism of disease, and because one may be required to develop a new model showing that that the oral inflammatory conditions and oral infections are successfully prevented by administration of the hydrogel of claim 1, it would constitute an undue and unpredictable search burden.
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 breadth of the claims and the nature of the invention, Applicants fail to provide information sufficient to practice the claimed invention for a hydrogel comprising chitosan for use in the prevention of an oral inflammatory condition and/or an oral infection and for a method of preventing an oral inflammatory condition and/or an oral infection comprising applying a hydrogel comprising chitosan as defined in claim 1 to an oral surface in a subject in need thereof.
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 10, 12, 13, 16, and 18 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 10, 12, 13, and 18, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For the purposes of expedited prosecution, these claims are examined without the limitations following the phrase “such as.”
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.
Claim 14 is 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.
Claim 14 depends from claim 1 and requires said hydrogel is used together with a brush, said brush comprising bristles comprising or consisting of chitosan. As stated in the above claim interpretation section, the limitation “for use in the treatment and/or prevention of an oral inflammatory condition and/or an oral infection and/or for use in endodontic treatment” is interpreted as an intended use of the hydrogel of claim 1 and does not limit the structure of this hydrogel. Therefore, claim 14, which further limits the use of the hydrogel by requiring said brush, does not further limit the structure of the hydrogel recited in claim 1, and therefore does not further limit the subject matter of the claim upon which it depends.
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
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)(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.
Claims 1, 6, 10, and 13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Furuike (Furuike, T.; et al. International Journal of Biological Macromolecules 2017, vol. 104, pp. 1620-1625; cited in IDS received September 15, 2023).
Furuike teaches a method of preparing a chitosan hydrogel wherein 1.0 g of chitosan is dissolved in 100 mL of 0.5 M acetic acid, a sodium hydroxide solution added to the chitosan solution pH reached 8.5–9.0, the obtained hydrogel decanted and washed with water, dialyzed against water, centrifuged at 14,000 rpm for the removal of excess water and suspended with a blender to afford a homogeneous gel (p. 1621, left column, Section 2.2).
Furuike further teaches the chitosan hydrogel containing 1 mmole of sugar units was suspended in deionized water 100 mL and acid solutions, such as acetic acid, were titrated into the hydrogel suspension (p. 1621, Section 2.3, lines 3-8). Furuike further teaches that the addition of acetic acid reduces the pH of the hydrogel to between pH 4 and 5 (p. 1622, Figure 3, see top left plot).
Regarding claim 10, because Furuike does not teach addition of an antimicrobial agent or a cross-linking agent in their hydrogels, Furuike anticipates claim 10.
Regarding claim 13, because the product of Furuike only includes chitosan, water, and pH regulators such as sodium hydroxide and acid, Furuike anticipates claim 13.
Thus Furuike anticipates claims 1, 6, 10, and 13.
Claims 1, 6, 10, and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yao (Yao, K. D.; et al. Journal of Applied Polymer Science 1993, vol. 48, pp. 343-354; cited in PTO-892).
Yao teaches the pH sensitivity of hydrogels based on a complex that forms between chitosan and a polyether network (p. 343, Title). Yang teaches preparation of their hydrogels by dissolving chitosan in 0.25 N acetic acid, mixing with polyether N330, adding glutaraldehyde under agitation, and incubating the mixture at 30°C for more than 6 h. Yao teaches the product was then washed with distilled water and dried (p. 344, left column, first paragraph, lines 1-7).
Yao further teaches the degree of swelling of their products prepared from different concentrations of chitosan at different pH values (p. 348, Figure 4), reaching a maximum degree of swelling at pH 3.19 (p. 347, right column, first paragraph, lines 4-6).
Regarding claim 10, because Yao teaches their hydrogel as including glutaraldehyde but not an additional antimicrobial agent, Yao also anticipates claim 10.
Thus Yao anticipates claims 1, 6, 10, and 19.
Claims 1, 6, 9, 10, and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kim (Kim, S. J.; et al. Reactive and Functional Polymers 2003, vol. 55, pp. 53-59; cited in PTO-892).
Kim teaches the swelling behavior of interpenetrating polymer network hydrogels composed of poly(vinyl alcohol) and chitosan (p. 53, Title). Kim teaches that chitosan in their hydrogels had an average molecular weight of 2.0 x 105, which is interpreted herein as equivalent to 200 kD (p. 54,right column, section 2.1).
Kim further teaches the equilibrium swelling ratio of their hydrogels prepared from different ratios of chitosan and PVA (abbreviated as IPN1-3, see p. 55, Table 1) in various pH buffer solutions including at buffers at pH 2 and pH 4, with the greatest swelling at pH 2 (p. 57, Figure 4).
Regarding claim 10, because Kim teaches their hydrogel as including the cross-linking agent acryloyl chloride (p. 54, right column, section 2.2, lines 3-4) but not an additional antimicrobial agent, Kim also anticipates claim 10.
Thus Kim anticipates claims 1, 6, 9, 10, and 22.
Claims 1, 6, 9, 10, 11, and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Delmar (Delmar, K.; et al. Carbohydrate Polymers 2015, vol. 127, pp. 28-37; cited in PTO-892).
Delmar teaches chitosan hydrogels crosslinked with genipin (p. 28, Abstract, lines 1-2).
Delmar teaches that chitosan used in their method had a weight averaged molecular weight of 207 kDa and viscosity average molecular weight Mv of 151 kDa (p. 29, right column, Section 2.1, lines 4-6).
Delmar teaches that a known amount of chitosan was dissolved in 2% aqueous acetic acid to obtain a final concentration of 1% (w/v). Delmar teaches the pH of each sample was elevated very slowly using NaOH under constant stirring while avoiding immediate precipitation caused by rapid pH increase, until achieving the desired pH value of 4.00, 4.50, 5.00, or 5.50 (p. 30, left column, section 2.4).
Delmar teaches a phase diagram of chitosan hydrogels (0.52–1.8%, w/v) crosslinked with genipin (0.005–0.4%, w/v) in a fixed pH value of 4.50 after curing for (A) 24 h and (B) 65 h (p. 31, Figure 1 caption; see Figures 1A and 1B). Delmar teaches that all concentrations of chitosan tested were able to form a gel structure with specific levels of genipin. (p. 31, Figure 1B).
Regarding claim 10, because Delmar teaches their hydrogel as including the cross-linking agent genipin but not an additional antimicrobial agent, Delmar also anticipates claim 10.
Thus Delmar anticipates claims 1, 6, 9, 10, 11, and 22.
Claims 1, 6, 10, and 13 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Marteinsson (U.S. pre-grant publication no. US 20180296724 A1; cited in IDS received September 15, 2023).
Marteinsson teaches chitosan-containing formulations with uses that include oral or dental administration for the purposes of disease prevention or treatment (cover page, Abstract, lines 1-12).
Specifically, Marteinsson teaches and claims an aqueous chitosan-containing formulation comprising: chitosan, in a range of 0.1 % to 10% by weight, based on the weight of the formulation, wherein 1% of the chitosan on a dry basis, in 1% acetic acid, has a Brookfield rotational viscosity at 25° C from 3000 cps to 9000 cps; an amount of at least one acid; and water (p. 10, claim 1). Marteinsson further teaches and claims the has a pH in the range of 3-5.9 (p. 10, claim 16).
Marteinsson teaches that products with rotational viscosities of about 1000 cps up to about 20,000,000 cps result in homogeneous gel-like products (p. 1, [0026], lines 1-6). Accordingly, the aqueous chitosan-containing formulation of Marteinsson with chitosan having a rotational viscosity of 3000 cps to 9000 cps is interpreted herein as a hydrogel, absent evidence to the contrary.
Therefore, given the considerable overlap in pH values recited in present claim 1 and claimed by Marteinsson, as well as the gel-like chitosan-containing formulation claimed by Marteinsson, Marteinsson is interpreted herein as anticipating claim 1. In addition, the considerable overlap in range of pH values claimed by Marteinsson and recited in present claim 6 is also interpreted as satisfying the limitations of claim 6.
MPEP 2131.02 states: “A reference disclosure can anticipate a claim when the reference describes the limitations but "'d[oes] not expressly spell out' the limitations as arranged or combined as in the claim, if a person of skill in the art, reading the reference, would ‘at once envisage’ the claimed arrangement or combination." Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 1381, 114 USPQ2d 1250, 1254 (Fed. Cir. 2015).” In this instance, because Marteinsson teaches and claims gels that satisfy the limitations of claim 1 and further claims pH values of said gels from 3 to 5.9, one of ordinary skill in the art would have at once envisaged the chitosan composition of Marteinsson with, for example, a pH between 3 and 5.
Regarding claim 10, in the absence of Marteinsson teaching inclusion of an antimicrobial agent or a cross-linking agent, Marteinsson also anticipates present claim 10.
Regarding claim 13, the acid claimed by the formulation of Marteinsson is reasonably considered as a pH regulator, and thus Marteinsson anticipates claim 13.
Thus Marteinsson anticipates claims 1, 6, 10, and 13.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 6-11, 13-14, 16, and 19-22 are rejected under 35 U.S.C. 103 as being unpatentable over Marteinsson (U.S. pre-grant publication no. US 20180296724 A1; cited in IDS received September 15, 2023).
The examiner believes that claims 1, 6, 10 and 13 are anticipated by Marteinsson, as described in the above rejection under 35 U.S.C. 102. However, for the sake of argument, if Marteinsson does not anticipate claims 1, 6, 10, and 13 because, for example, some parts of the range of pH values claimed by Marteinsson fall outside of the range of pH values of the present claims, then these claims would have been obvious over Marteinsson.
Marteinsson teaches chitosan-containing formulations with uses that include oral or dental administration for the purposes of disease prevention or treatment (cover page, Abstract, lines 1-12).
Specifically, Marteinsson teaches and claims an aqueous chitosan-containing formulation comprising: chitosan, in a range of 0.1% to 10% by weight, based on the weight of the formulation, wherein 1% of the chitosan on a dry basis, in 1% acetic acid, has a Brookfield rotational viscosity at 25° C. from 3000 cps to 9000 cps; an amount of at least one acid; and water (p. 10, claim 1). Marteinsson further teaches and claims the has a pH in the range of 3-5.9 (p. 10, claim 16).
Marteinsson further teaches that products with rotational viscosities of about 1000 cps up to about 20,000,000 cps result in homogeneous gel-like products (p. 1, [0026], lines 1-6). Accordingly, the aqueous chitosan-containing formulation of Marteinsson may in the form of a hydrogel.
Regarding the molecular weight of the chitosan used to prepare the formulations of Marteinsson, Marteinsson teaches that methods of producing chitosan solutions having a Brookfield rotational viscosity in the range of about 1000 cps up to about 20,000,000 cps resulting in a homogeneous gel-like product comprise mixing about 0.5% up to about 5% chitosan with an amount of acidified water effective to solubilize said chitosan, wherein said chitosan has a weight-average molecular weight of from about 200,000 Daltons to about 2,000,000 Daltons, an apparent viscosity of at least about 100 cps, and a percentage of deacetylation of from about 70% to 100% (p. 5, [0116]-[0121]). Therefore, Marteinsson teaches that chitosan with a weight-average molecular weight of from about 200,000 Daltons to about 2,000,000 Daltons forms a gel-like product in their method.
In addition, Marteinsson teaches specific chitosan-containing formulations. As one example, Marteinsson teaches the formulation of example 1, wherein 11.36 g of 88% lactic acid is mixed with 954.36 g of deionized water, to which 22.52 g of chitosan powder adjusted for a moisture content of 10.5% with viscosity of 3000-9000 cps is solubilized with heating at 60 °C and stirring for at least 30 minutes (p. 8, right column, Example 1, [0183]-[0185]).
Assuming the lactic acid and chitosan powder are both in solution with water, and thus accounting for this moisture in lactic acid and chitosan, the above composition comprises 10.0 g of lactic acid (with a remaining 1.36 g of water), 20.16 g of chitosan (with a remaining 2.36 g of water), and 958.1 g of water (which includes the water from the lactic acid and chitosan). The total mass of this composition is 988.26 g, and thus includes 1.01 wt% lactic acid and 2.04 wt% chitosan. This composition thus satisfies the requirements recited in claims 8, 11, and 13.
Moreover, Marteinsson teaches that this product is used as a transparent, flexible bandage (p. 8, [0185], line 7) and refers to this product as a gel in examples 1a, 1b, and 1c. In example 1a, Marteinsson teaches that chitosan gel was applied daily to cover a laceration wound (p. 8, [0186]). In example 1b, Marteinsson teaches that chitosan gel was applied daily to a burn wound 25 days post-accident (p. 8, [0187]-[0188]lines 1-2). In example 1c, Marteinsson teaches that chitosan gel was applied to one of the two belly cuts resulting from a laparoscopic appendectomy (p. 9, [0189], lines 1-2). Therefore, this product of example 1 is reasonably interpreted herein as a gel.
Marteinsson further teaches the composition of Example 3 (p. 9, right column, [0196]-[0200]). In this example, 20.98 g if glacial acetic acid is mixed with 979.02 g deionized water and 50.00 g chitosan powder on a dry basis (10-100 cps, 75-85% DDA) is slowly added to solubilize the chitosan properly while gently heating the solution with stirring (p. 9, [0196]-[0200]). Marteinsson teaches the formulation can be prepared with slight variations to reach the desired viscosity and acidity level (p. 9, [0196]).
Glacial acetic acid is interpreted herein as anhydrous acetic acid, which the examiner believes is reasonable as evidenced by Sigma Aldrich teaching glacial acetic acid as ≥99% acetic acid (Sigma-Aldrich product specification sheet for glacial acetic acid; cited in PTO-892). Therefore, this composition includes 20.98 g of acetic acid, 979.02 g of deionized water, and 50.00 g of chitosan powder, which corresponds with 2.0 wt% acetic acid and 4.7 wt% chitosan. This composition thus satisfies the requirements recited in claims 8, 11, 13, and 21, wherein 4.7 wt% is considered as about 4.5 wt%.
Finally, Marteinsson teaches that their invention provides methods of promoting gum health (for example, by inhibiting the growth of oral bacteria) by orally administering a composition of the invention and provides methods of treating peri-implantitis by orally or dentally administering to a subject the compositions of their invention (p. 2, left column, first paragraph, lines 2-10).
Marteinsson does not teach a specific embodiment that includes all limitations of present claim 1, specifically a that includes the pH of a chitosan-containing hydrogel as between 2.5 and 5.2.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application for one of ordinary skill in the art to modify an aqueous chitosan-containing composition in the form of a gel taught by Marteinsson to have a pH between 3 and 5.2, as required by present claim 1. One of ordinary skill in the art would have been motivated to modify an aqueous chitosan-containing composition in the form of a gel taught by Marteinsson to have a pH between 3 and 5, as required by present claim 1, because Marteinsson teaches the formulation of example 1, presents examples in which it is used as a gel for the purposes of treating a laceration (Example 1a), a burn wound (Example 1b), and as a treatment for wound healing and scar healing after surgery (Example 1c), , and finally teaches and claims the pH of their chitosan composition is in the range of 3-5.9. Although Marteinsson does not disclose the pH of the formulation of Example 1, one of ordinary skill in the art would have contemplated adjusting the pH, if it fell outside of the range of 3-5.9, to within said range. Furthermore, in view of the considerable overlap of the pH values recited by Marteinsson with those recited in claims 1, 6, and 19, one of ordinary skill in the art would have contemplated compositions within the full range of pH values recited by Marteinsson, because hydrogels of different pH values may have impacted the efficacy of the gel composition used for wound healing.
Regarding the viscosity of the hydrogel required by claims 7 and 20, Marteinsson teaches that products with rotational viscosities of about 1000 cps up to about 20,000,000 cps result in homogeneous gel-like product. As evidenced by NIST (NIST Special Publication 1038, 2006; cited in PTO-892), 1 centipoise is equivalent to 1 mPas (p. 12, Section 5.2.10). Therefore, a gel of viscosity 3000 cps, as claimed by Marteinsson, would satisfy the viscosity limitations of claim 7. In addition, because Marteinsson teaches that products of viscosities of about 1000 cps also form gels, one of ordinary skill in the art would have reasonably contemplated a gel product with viscosity of 1000 cps.
Regarding the concentration of chitosan required by claims 8 and 21, the formulations of Examples 1 and 3 of Marteinsson include concentrations of chitosan that satisfy the limitations of claim 8. In addition, because claim 21 recites an upper limit of about 4.5 wt%, the formulation of Example 3 of Marteinsson, which includes 4.7 wt% chitosan, is interpreted as satisfying the limitations of claim 21.
However, if 4.7% is considered as outside of the range of “about 4.5 wt%,” because Marteinsson teaches and claims chitosan in a range of 0.1-10% and teaches examples both below and above the range recited in claim 21, one of ordinary skill in the art would have reasonably contemplated a formulation of Marteinsson with about 3.5 to about 4.5 wt% chitosan.
Regarding the molecular weight of chitosan of claims 9 and 22, although Marteinsson does not disclose the molecular weight of chitosans used in Examples 1 and 3, because Marteinsson teaches chitosans with molecular weight of 200,000 Daltons to about 2,000,000 Daltons may be used to produce homogenous gels using their methods, one of ordinary skill in the art would have contemplated Examples 1 and 3 using chitosans of the full range of molecular weights taught by Marteinsson, which would thus render obvious claims 9 and 22.
Regarding claim 10, because Marteinsson teaches Example 1 that consists solely of chitosan, water, and lactic acid, a chitosan composition analogous to Example 1 with a pH value between 3.5 and 5.2, obvious over Marteinsson as described above, also satisfies the limitations of claim 10 wherein the hydrogel does not comprise an additional antimicrobial agent or a cross-linking agent.
Regarding claim 11, each of the formulations of Examples 1 and 3 satisfy the limitations of claim 11, and thus a hydrogel analogous to that of Example 1 or 3 with a pH value between 3.5 and 5.2, obvious over Marteinsson as described above, would satisfy the requirements of claim 11.
Regarding claim 13, because Marteinsson teaches Examples 1 and that consists solely of chitosan, water, and a pH regulator (lactic acid or acetic acid), a chitosan composition analogous to Example 1 or 3 with a pH value between 3.5 and 5.2, obvious over Marteinsson as described above, would satisfy the requirements of claim 13.
Regarding claim 16, because Marteinsson renders obvious a composition that satisfies the hydrogel of claim 1, as described above, and because Marteinsson further suggests this composition as useful for treating peri-implantitis by dentally administering a composition of Marteinsson, one of ordinary skill in the art would have reasonably contemplated orally or dentally administering a composition of Marteinsson for the purposes of treating peri-implantitis. Treating peri-implantitis is reasonably considered as use in endodontic treatment, and orally or dentally administering is interpreted herein as applying the hydrogel to an oral surface, as required by claim 16.
Therefore the invention taken as a whole is prima facie obvious.
Claims 14 and 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Marteinsson as applied to claims 1, 6-11, 13-14, 16, and 19-22 above, and further in view of Lyngstadaas (U.S. pre-grant publication no. US 20140295378 A1; cited in PTO-892).
Marteinsson teaches as described in the above rejections under 35 U.S.C. 102 and 35 U.S.C. 103. Specifically, Marteinsson teaches the hydrogels above and their use for promoting gum health and for treating peri-implantitis by oral or dental administration.
Marteinsson does not teach the wherein the hydrogel is used together with a brush, said brush comprising bristles comprising or consisting of chitosan, as recited in claim 14, a kit comprising a brush comprising bristles comprising chitosan and the hydrogel of claim 1, as required by claim 17, or the kit of claim 17 further comprising a device for applying said hydrogel to an oral surface, such as a tooth surface or a dental implant surface.
Lyngstadaas teaches that in patients with implants, a periodontitis-like condition may develop into a condition called peri-implantitis and is caused by the colonization of bacteria of the implants’ surface (p. 1, [0008], lines 1-4).
Lyngstadaas teaches that treatment of periodontal disease usually involves removing the bacterial deposits and dental calculus (p. 1, [0009], lines 1-2), and bacterial infections around implants are treated with debridement of the exposed surfaces (p. 1, [0010], lines 1-2).
Lyngstadaas teaches that the cleaning tools used for implant debridement leave contaminating material residues on the medical implant surface, or in the peri-implant tissue, and such material can cause a toxic reaction, foreign body reaction, or other inflammatory reaction that may further exaggerate the peri-implant disease and potentially induce further loss of implant attachment (p. 2, [0015], lines 1-8).
Lyngstadaas teaches and claims a debridement and/or implant cleaning tool (1) comprising an elongated base member (2) and means for cleaning (4) in a cleaning section (5) at a first end (6) of 5 said base member (2); wherein said means for cleaning (4) is in the form of bristles made of a bioresorbable polymer (p. 16, claim 1), and further claims the bioresorbable polymer is chitosan (p. 16, claim 10). Lyngstadaas teaches an embodiment wherein the debridement tool is a brush with bristles made of chitosan (p. 15, Example 5, [0171], lines 1-6) (emphasis added).
Finally, Lyngstadaas teaches their tool may be utilized together with a substance having a cleaning effect, such as a microbe growth inhibiting and/or microbe killing substance (p. 11, [0123], lines 1-7). Lyngstadaas teaches these substance(s) may be provided in a separate container with the tool in a kit of parts comprising a tool for application to the tool or the dental floss or tape and/or the surface to be debrided and/or cleaned (p. 11, [0123], lines 7-11).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to use the hydrogel of Marteinsson together with the brush disclosed by Lyngstadaas. One of ordinary skill in the art would have been motivated to use the chitosan-containing formulation of Marteinsson together with the brush disclosed by Lyngstadaas because Marteinsson teaches their formulation may be used for the purposes of treating peri-implantitis by oral or dental administration, and because Lyngstadaas teaches debridement on implant tissue is used for bacterial infections around implants and avoids potential issues that arise from leaving contaminating material residues on the medical implant surface. Accordingly, one of ordinary skill in the art would have recognized the debriding tool taught by Lyngstadaas comprising chitosan may be a superior debridement tool for treating peri-implantitis, and that is may be used with the chitosan formulation of Marteinsson for superior treatment of peri-implantitis.
Regarding the kit of claim 17, because Lyngstadaas teaches their brush may be included in a kit with a substance having a cleaning effect, such as a microbe growth inhibiting and/or microbe killing substance, it would have been prima facie obvious to one of ordinary skill in the art to specifically include gel for treating peri-implantitis of Marteinsson in a kit with the brush taught by Lyngstadaas. Regarding the kit of claim 18, because Lyngstadaas teaches the additional substance may be provided in a separate container for application to the tool and/or the surface to be debrided and/or cleaned, the requirement that the device for applying said hydrogel to an oral surface is also obvious over Marteinsson in view of Lyngstadaas.
Therefore the invention taken as a whole is prima facie obvious.
Claim 12 rejected under 35 U.S.C. 103 as being unpatentable over Marteinsson as applied to claims 1, 6-11, 13-14, 16, and 19-22 above, and further in view of Zubko (Zubko, E. I.; et al. BMC Research Notes 2013, vol. 6, 272; cited in PTO-892) and Ferreira (Ferreira, M. O. G.; et al. Journal of Drug Delivery Science and Technology 2019, vol. 49, pp. 375-382; cited in PTO-892).
Marteinsson teaches as described in the above rejections under 35 U.S.C. 102 and 35 U.S.C. 103. In addition, Marteinsson teaches the antibacterial activity of a 0.65% (w/w) chitosan lactate solution against P. aeruginosa and S. aureus (p. 2, [0038]; document p. 3, Figure 2).
Marteinsson does not teach the hydrogel of claim 1, wherein said hydrogel consists of water and/or an alcohol, such as ethanol, as a solvent, chitosan, chlorhexidine, hydrogen peroxide, iodine, and a pH regulator, as recited in claim 12.
Ferreira teaches that chitosan has chemical properties that allow the formation of gels in acid media, which can be used as a dressing for wound treatment, because they are biocompatible and have activity against pathogenic microorganisms, and further teaches a chitosan gel associated with chlorhexidine for the study of antibacterial and healing activity (p. 375, Abstract, lines 1-4). Ferreira teaches that a chitosan gel alone shows modest inhibition against S. aureus in a disc diffusion test, and that addition of chlorhexidine enhanced the antibacterial activity of chitosan and reduced the amount of chlorhexidine necessary to inhibit S. aureus growth (for example, at 2% chlorhexidine) (p. 378, left column, Table 2).
Zubko teaches the co-operative inhibitory activities (synergism, additive effects and modes of growth inhibition) of hydrogen peroxide and iodine used concurrently against 3 bacterial and 16 yeast species (p. 1, Abstract, Background section, lines 3-4). Zubko provides specific activities against all bacterial and yeast species (p. 2, Figure 1 and p. 4, Table 1), which include E. coli, S. aureus, and P. aeruginosa. Zubko teaches that the antibacterial activities of I2 and H2O2 were additive or synergistic against all species used in their study (p. 1, Results, Background section, lines 1-2).
It would have been prima facie obvious to one of ordinary skill in the art to modify the chitosan hydrogel of claim 1 obvious over Marteinsson with hydrogen peroxide, iodine, and chlorhexidine. One of ordinary skill in the art would have been motivated to art to modify the chitosan hydrogel of claim 1 obvious over Marteinsson with hydrogen peroxide, iodine, and chlorhexidine because Marteinsson teaches their chitosan-containing compositions comprising water, chitosan, and a pH regulator as having antibacterial properties, Zubko teaches the synergistic antibacterial properties of hydrogen peroxide and iodine, and Ferreira teaches chlorhexidine and chitosan as having antibacterial activity against S. aureus.
MPEP 2144.06 states: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
In this instance, because Marteinsson teaches their formulations as having utility as antibacterial compositions, and because each of Zubko and Ferreira teach compositions comprising hydrogen peroxide, iodine, and chlorhexidine as also having antibacterial activity, the modification of the composition of Marteinsson with hydrogen peroxide, iodine, and chlorhexidine is prima facie obvious, because each of these compositions may be used for the purposes of inhibiting or reducing bacterial growth, such as growth of S. aureus.
Therefore the invention taken as a whole is prima facie obvious.
Conclusion
No claims are allowed.
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/B.M.B./Examiner, Art Unit 1693
/ANDREA OLSON/Primary Examiner, Art Unit 1693