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 .
Claim Status
Claims 1-10, 14-22, and 25-28, are pending and under examination.
Claim Interpretation
The examiner best understands the limitation of a decrease in interleukin-1 expression to be a decrease in any of the isoforms of IL-1, including IL-1 beta or IL-1 alpha, as meeting the claimed limitations.
Claim Objections
Claims 3-10, 16-26, and 28, are objected to because of the following informalities: the text of the amended portions of claims 3-10, 16-26, and 28, are blurry and difficult to read. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) or pre-AIA 2nd ¶
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 5, 8, and 14-28, 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 5 recites collagen in an amount greater than about 50 mg and up to about 200 mg or less, and the limitation is unclear where greater than about 50 mg includes amounts above about 200 mg, and about 200 mg or less contains amounts below about 50 mg. For purposes of examination, the examiner best understands the limitation as about 50 mg to about 200 mg.
Claims 8, 18, and 27, recite green lipped mussel (Pernia canaliculus), turmeric (Curcuma longa), stinging nettle (Urtica dioica), and Cat’s claw (Uncaria tomentosa), and it is unclear if the parenthetical terms are intended to define the particular source of the preceding term, another name of the preceding term, or an example of the preceding term.
Claim 28 is rejected for the same reasons for depending upon rejected claim 27.
Claim 14 recites a method of improving one or more of joint pain and inflammation in mammal comprising “supplying” to the mammal the composition as claimed. Where “supplying” is not defined, it is unclear what constitutes supplying to a mammal. For example, is the composition given to the mammal without administration? If so, it is unclear how joint pain, or inflammation can be improved if the composition is not administered. For purposes of examination, the claim is interpreted as administered.
Claims 15-26 are rejected for the same reasons for depending upon rejected claim 14.
The term “subjective reduction” in claim 15 is a relative term which renders the claim indefinite. The term “subjective reduction” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Here, the claim and specification do not provide criteria, a threshold, pain scale, assessment method, or other guidance for determining when a subjective reduction in join pain has occurred. This would also be expected to vary depending on the pain tolerance of the subject.
Claim 16 recites a collagen amount of at least 0.3 mg/kg of body weight per day to about 3 mg/kg of bodyweight per day. The limitation is unclear where at least 0.3 mg/kg includes amounts above about 3 mg/kg of bodyweight per day. For purposes of examination, the examiner best understands the limitation to be 0.3 mg/kg to about 3 mg/kg of body weight per day.
Claim 20 recites wherein the improvement in one or more of joint pain and inflammation is evidenced in about one week or less, and the limitation is unclear where it is not clear how the improvement is to be evidenced. For example, is it a certain decrease in a particular expression level, a subjective measurement, or something else? For purposes of examination, any improvement as measured by any means is interpreted to meet the claimed limitation.
Claim Rejections - 35 USC § 112(d) or pre-AIA 4th ¶
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 15, 21, and 22, 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.
Claim 15 and 21 recite a decrease in serum interleukin-1, interleukin-6, TNF-alpha, COX-2, SOX-9, MMP-3, or a combination thereof. The claims depend from claim 14, where there is no recitation of SOX-9 or MMP-13. Accordingly, where the claim recites additional expressions not recited in claim 14, and where claims 15 and 21 allow for SOX-9 or MMP-13 inhibition without the others, the limitation fails to include all limitations of the parent claim and recite a further limitation.
Claim 22 recites wherein the improvement is evidenced by a decrease in matrix metallopeptidase 13 serum. The claim depends from claim 14 where there is no recitation of matrix metallopeptidase 13 serum. Accordingly, where the claim recites additional expressions not recited in claim 14, and where claim 22 allow for matrix metallopeptidase 13 serum decrease without a decrease in the others recited in claim 14, the limitation fails to include all limitations of the parent claim and recite a further limitation.
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.
Claim 27 is rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by She (CN 109010805 A, cited on IDS dated 07/29/2024).
She teaches compositions containing type II collagen and turmeric and/or curcumin extracted from turmeric, where the combination can be applied to a variety of inflammatory disease, including arthritis, making the treatment effect better (¶¶ 5-7, 12). Particular embodiments are disclosed comprising type II collagen and the curcumin extracted from turmeric (ex. 4).
Claim Rejections - 35 USC § 103
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 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.
Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over She (CN 109010805 A, cited on IDS dated 07/29/2024), and Li et al (Inflammation, 2017. vol 5, no 5, pp. 1599-1605, hereinafter “Li”).
She teaches compositions containing type II collagen and turmeric and/or curcumin extracted from turmeric, where the combination can be applied to a variety of inflammatory disease, including arthritis, making the treatment effect better (¶¶ 5-7, 12). Particular embodiments are disclosed comprising type II collagen and the curcumin (ex. 4). Type II collagen can relieve joint pain, prevent, and treat osteoarthritis (¶ 5). Type II collagen can be denatured or non-denatured (¶ 12). Turmeric has anti-inflammatory effects and can improve arthritis and inflammatory-related disease (¶ 6). The compositions reduced IL-1 beta and TNF-alpha expression levels (Table 2).
She does not teach wherein the extract and or isolate is from those of claim 28.
Li teaches andrographolide from Andrographis paniculata exhibits anti-inflammatory activity in arthritis (abs). Andrographolide treatment significantly reduced the production of serum anti-collagen II antibody, TNF-alpha, IL-1 beta, and IL-6 (abs, pg. 1603 1st col 2nd ¶, fig. 3, 5).
It would have been obvious to modify the composition of She by selecting from other known anti-inflammatory active agents that were known to significantly reduce IL-1 beta, TNF-alpha, etc., expression levels in arthritis, such as andrographolide from Andrographis paniculata, as taught by Li. The skilled artisan would have had a reasonable expectation of success where She and Li are both directed to composition capable of reducing IL-1 beta and TNF-alpha expression levels in joint inflammation due to arthritis.
Claims 1-8, 14-18, 20-22, 25, and 26, are rejected under 35 U.S.C. 103 as being unpatentable over She (CN 109010805 A, cited on IDS dated 07/29/2024), in view of Hingorani et al (US 20170333362 A1, hereinafter “Hingorani”), as evidenced by Westeson et al (US 6207178 B1, hereinafter “Westeson).
She teaches compositions containing type II collagen and turmeric and/or curcumin extracted from turmeric, where the combination can be applied to a variety of inflammatory disease, including arthritis, making the treatment effect better (¶¶ 5-7, 12). Type II collagen can relieve joint pain, prevent, and treat osteoarthritis (¶ 5). Turmeric has anti-inflammatory effects and can improve arthritis and inflammatory-related disease (¶ 6). Type II collagen can be denatured or non-denatured (¶ 12). The compositions contain 15-1050 parts by weight of type II collagen, 5-80 parts by weight of curcuminoids, and 500-1500 parts by weight of an active protective agent (¶ 14). Other embodiments may comprise 15-50 parts by weight of undenatured type II collagen and/or 500-1000 parts by weight of denatured type II collagen, 10-50 parts by weight of curcuminoids, and 500-1000 parts by weight of an active protectant, and are formulated into tablets (¶ 15). Each tablet weighing 1.0 to 2.0 g (¶ 27). Ex. 4 comprises 50g non-denatured type II collagen, 10g curcumin, 600g mannitol, 400g dextrin, 15g magnesium stearate, 10g silicon dioxide, 40g 30% (v/v) aqueous ethanol solution, 40g croscarmellose sodium, 20g aspartame, 30g water-soluble natural flavoring, with a tablet weight of 1.5 g (ex. 4). The drugs were administered once per day (¶ 116). Table 2 tests each embodiment, model group, and control, on the expression of IL-1beta and TNF-alpha in the blood or arthritic mice, where the treatment groups showed significant reductions in both IL-1beta and TNF-alpha after 2 weeks (Table 2). The IL-1beta model group expressed 28.26 +/- 6.29 pg/mL, whereas the treatment groups ranged from 15.91 +/-3.87 to 17.54 +/- 3.51 pg/ml (Table 2). The TNF-alpha model group expressed 27.43 +/- 6.48 pg/ml, whereas the treatment group ranged from 14.46 +/- 3.26 to 16.22 +/- 3.54 pg/ml (Table 2). Embodiments that did not contain turmeric had a suboptimal effect in treating inflammation (¶ 129). The compositions were administered daily (¶ 116).
She does not teach a lipid mulitiparticulate, nor an explicit embodiment as claimed with the expression level reduction of claims 21 and 22.
Hingorani teaches stable solid lipid particle compositions for improved bioavailability of lipophilic compounds for age-related diseases, including osteoarthritis (abs, ¶¶ 7, 54). The compositions comprise a plurality of solid lipid microparticles containing an active ingredient in their core or embedded in the solid lipid microparticles (¶ 51). As evidenced by Westeson, solid lipid particles comprising a lipid matrix (abs, col 6 2nd ¶). Curcumin, a turmeric extract, is a potent antioxidant and anti-inflammatory agent acting on pro-inflammatory mediators including COX-2, iNOS, il-I and TNFα (¶¶ 4, 5). Boswellic acids (Boswellia serrata) have anti-inflammatory properties and are traditionally used for the treatment of osteoarthritis (¶ 183). Curcumin as a turmeric extract and boswellic acid were known to have poor bioavailability, stability, solubility, and permeability of the active in the gut (¶¶ 12, 183). The lipid microparticles comprise about 15-40% of at least one active compound (¶ 46, claim 22). The boswellic acid embodiments caused a marked lowering of IL-2 and LL-4 levels compared to baseline and was effective in modulating inflammatory cytokines (¶¶ 185-189). The lipid particles may be formulated into any suitable oral nutraceutical or pharmaceutical dosage forms including, but not limited to, tablets, capsules, powders, liquids, etc. (¶ 89). In embodiments, the formulations contained 100 mg of 40% boswellic acid (¶ 185).
Regarding claim 1, it would have been obvious to formulate a composition comprising an extract of turmeric and undenatured type II collagen, where the combination was known to have improved effect in arthritis and inflammatory-related disease, and where the combination was capable of reducing expression levels of IL-1beta and TNF-alpha.
Regarding the lipid multiarticulate of claim 1, it would have been obvious to include the extract of turmeric of She in a plurality of solid lipid microparticles, where the particles were known to improve the bioavailability, stability, solubility, and permeability of the active in the gut, as taught by Hingorani. The examiner notes that while the plurality of solid lipid particles are not specifically defined as a “lipid multiarticulate”, where the particles comprise a plurality of particles (i.e., multiple particles), are lipidic, and comprise the active agent embedded or in the core of each lipid particle (i.e., lipid matrix), it appears the limitation of a lipid multiarticulate as claimed is met. Purely arguendo, if the active agent embedded or in the core of the particles are not dispersed, it would have been well within the relative skills of the skilled artisan to have dispersed the active agent in the lipid matrix, where the skilled artisan would reasonably recognize dispersing the active agent would result in a more consistent release profile, depending on the desired use of the composition.
Regarding claim 2, where the composition made obvious above comprises the active agent embedded or present within the core of the lipid particles (i.e., in the lipid matrix), it appears the active agent is encapsulated by the lipid matrix.
Regarding claim 3, where Hingorini teaches the lipid microparticles comprise about 15-45% of the at least one active compound, wherein the active compounds may be selected from curcumin as a turmeric extract, it would have been obvious to include the extract of turmeric in the lipid multiarticulate in an amount of about 15-45% of the particles, falling within the claimed range.
Regarding claim 4, it would have been obvious to formulate the composition in the form of a tablet, as taught by She. Further, the skilled artisan would have had a reasonable expectation of success in formulating the lipid particles in a tablet where the lipid particles of Hingorini are taught to be suitable for tablet formulations.
Regarding claim 5, it would have been obvious to formulate the composition made obvious above with undenatured type II collagen in amounts from the working examples of She, such as 61.72 mg undenatured type II collagen ((50 g/1215 g) x 1.5 g = 61.72 mg/tablet) from example 4, falling within the claimed range.
Regarding claim 6, it would have been obvious to formulate the composition made obvious above with an amount of curcumin as an extract of turmeric from the working examples of She, such as 12.35 mg undenatured type II collagen ((10 g/1215 g) x 1.5 g = 12.35 mg/tablet) from example 4, falling within the claimed range.
Regarding claim 7, where undenatured type II collagen is made obvious above, the limitation is met.
Regarding claim 8, the composition made obvious above comprises an extract of turmeric, thereby meeting the claimed limitation.
Regarding claim 14, it would have been obvious to administer a therapeutically effective amount of the composition made obvious above to improve joint pain or inflammation, where She and Hingorani are both directed to compositions for treating osteoarthritis by administering anti-inflammatory agents to a subject.
Regarding claim 15, where the She teaches the combination of turmeric and type II collagen decreased expression levels of IL-1beta from 28.26 +/- 6.29 pg/mL in the model group to 15.91 +/-3.87 to 17.54 +/- 3.51 pg/ml for the treatment groups, and decreased expression levels of TNF-alpha from 27.43 +/- 6.48 pg/ml in the model group to 14.46 +/- 3.26 to 16.22 +/- 3.54 pg/ml for the treatment groups, the decrease in IL-1beta was up to about 33.8% and the decrease in TNF-alpha was up to about 33%, the ranges overlapping those instantly claimed. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding claim 17, where undenatured type II collagen is made obvious above, the limitation is met.
Regarding claim 18, were an extract of turmeric is made obvious above, the claimed limitations are met.
Regarding claim 20, where She teaches administration of the composition results in an improvement in inflammation, as evidenced by the reduction in IL-1beta and TNF-alpha expression levels after two weeks of treatment, the skilled artisan would reasonably expect that at least some improvement in inflammation would occur within the first week, where the collagen and turmeric were known anti-inflammatory agents. Purely arguendo, if not, it would have been obvious for the skilled artisan to have routinely optimized the duration of treatment, amount of collagen and active agent, depending on the desired anti-inflammatory or pain reduction effects for desired treatments and severity of the condition to be treated. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2144.05(II)(A).
Regarding claim 21, where She teaches administration of the composition results in an improvement in inflammation, as evidenced by the reduction in IL-1beta and TNF-alpha expression levels after two weeks of treatment of up to 33.8% and 33% respectively, it would have been well within the relative skills of the skilled artisan to have routinely optimized the duration of treatment, amount of collagen and active agent, depending on the desired anti-inflammatory marker reduction or pain reduction effects for desired treatments and severity of the condition to be treated. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2144.05(II)(A).
Regarding claim 22, where the composition of the method made obvious above showed a decrease in serum IL-1beta of 33.8%, it appears that the limitation of a reduction in interleukin-1 of at least about 20% is met. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding claim 26, it would have been obvious to administer the composition made obvious above daily, as taught by She.
Claims 9, 10, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over She (CN 109010805 A, cited on IDS dated 07/29/2024) and Hingorani et al (US 20170333362 A1, hereinafter “Hingorani”), as applied to claims 1-8, 14-18, 20-22, 25, and 26 above, and further in view of Wang et al (Osteoarthritis and Cartilage, 2014, vol 22, issue 1, pp. 128-132, hereinafter “Wang”).
She and Hingorani are discussed above, and while Hingorani teaches boswellic acid modulates inflammatory cytokines with a reduction in IL-2 and IL-4, and IL-1 and TNF-alpha were tested, the reference does not explicitly state a reduction in the expression levels of those instantly claimed.
Wang teaches boswellic acid, especially acetyl-11-keto-beta-boswellic acid, attenuates osteoarthritis, has anti-inflammatory effects, and suppresses production; of IL-1 beta, TNF-alpha, etc. (abs, pg. 129 1st col 1st ¶, fig. 2).
Regarding claims 9 and 19, it would have been obvious to modify the composition and method made obvious above by selecting from other known anti-inflammatory active agents that were known to modulate inflammatory cytokines for osteoarthritis, such as boswellic acid (Boswellia serrata), as taught by Hingorani, and where boswellic acid was known to specifically reduce IL-1 beta and TNF-alpha expression levels in osteoarthritis, as taught by Wang. The skilled artisan would have had a reasonable expectation of success where She, Hingorani, and Wang are all directed to composition capable of reducing inflammation in joints.
Regarding claim 10, it would have been obvious to include boswellic acid comprising acetyl-11-keto-beta-boswellic acid in known amount suitable for anti-inflammatory compositions capable of treating osteoarthritis, such as 40 mg, as taught by Hingorani, falling within the claimed range.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over She (CN 109010805 A, cited on IDS dated 07/29/2024) and Hingorani et al (US 20170333362 A1, hereinafter “Hingorani”), as applied to claim 1-8, 14-18, 20-22, 25, and 26 above, and further in view of Mannelli et al (BMC Musculoskelet Discord, 2013, 14:228, pp. 1-9, hereinafter “Mannelli”).
She and Hingorani are discussed above but do not specifically teach the mg/kg of collagen per day.
Mannelli teaches type II collagen was known to be administered at 1, 3, and 10 mg/kg to relieve and prevent pain in osteoarthritis (abs).
It would have bene obvious to modify the method made obvious above by including known collagen concentrations suitable for reducing pain in osteoarthritis, such as 1 or 3 mg/kg, where She, Hingorani, and Mannelli are all directed to improving pain or inflammation in osteoarthritis. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over She (CN 109010805 A, cited on IDS dated 07/29/2024) and Hingorani et al (US 20170333362 A1, hereinafter “Hingorani”), as applied to claim 1-8, 14-18, 20-22, 25, and 26 above, and further in view of Acharya et al (WO 2021111312 A1, hereinafter “Archarya”).
She and Hingorani are discussed above but do not teach a Kellgren-Lawrence score specifically.
Acharya teaches stable curcumin compositions for prevention and maintenance of arthritis and osteoarthritis, wherein the curcumin is an extract from Curcuma longa (abs, pg 1 ln 19-20). Administration of curcumin was known to decrease the Kellgren-Lawrence score in osteoarthritis, with a reduction of greater than 20% for both 100 mg/kg and 200 mg/kg curcumin administration (fig. 7B).
Where the composition made obvious above is directed to decreasing inflammation or pain associated osteoarthritis, and the combination of collagen and turmeric and/or curcumin as an extract of turmeric was known to reduce inflammation, it would have been obvious to formulate the composition made obvious above in a sufficient amount suitable to decrease the Kellgren-Lawrence score of greater than 20%, where curcumin as an extract of Curcuma long was known to cause reductions in Kellgren-Lawrence scores falling within the claimed range. Further, it would have been well within the relative skilled of the skilled artisan to have routinely optimize the amount of the composition, the concentration of the active agent, etc., in order to achieve desired reduction in Kellgren-Lawrence score. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2144.05(II)(A).
Claims 1-8, 14-18, 20-22, 25, and 26, are rejected under 35 U.S.C. 103 as being unpatentable over She (CN 109010805 A, cited on IDS dated 07/29/2024), in view of Hingorani et al (US 20170333362 A1, hereinafter “Hingorani”) and Diorio et al (US 20170354599 A1, hereinafter “Diorio”), as evidenced by Westeson et al (US 6207178 B1, hereinafter “Westeson).
She teaches compositions containing type II collagen and turmeric and/or curcumin extracted from turmeric, where the combination can be applied to a variety of inflammatory disease, including arthritis, making the treatment effect better (¶¶ 5-7, 12). Type II collagen can relieve joint pain, prevent, and treat osteoarthritis (¶ 5). Turmeric has anti-inflammatory effects and can improve arthritis and inflammatory-related disease (¶ 6). Type II collagen can be denatured or non-denatured (¶ 12). The compositions contain 15-1050 parts by weight of type II collagen, 5-80 parts by weight of curcuminoids, and 500-1500 parts by weight of an active protective agent (¶ 14). Other embodiments may comprise 15-50 parts by weight of undenatured type II collagen and/or 500-1000 parts by weight of denatured type II collagen, 10-50 parts by weight of curcuminoids, and 500-1000 parts by weight of an active protectant, and are formulated into tablets (¶ 15). Each tablet weighing 1.0 to 2.0 g (¶ 27). Ex. 4 comprises 50g non-denatured type II collagen, 10g curcumin, 600g mannitol, 400g dextrin, 15g magnesium stearate, 10g silicon dioxide, 40g 30% (v/v) aqueous ethanol solution, 40g croscarmellose sodium, 20g aspartame, 30g water-soluble natural flavoring, with a tablet weight of 1.5 g (ex. 4). The drugs were administered once per day (¶ 116). Table 2 tests each embodiment, model group, and control, on the expression of IL-1beta and TNF-alpha in the blood or arthritic mice, where the treatment groups showed significant reductions in both IL-1beta and TNF-alpha after 2 weeks (Table 2). The IL-1beta model group expressed 28.26 +/- 6.29 pg/mL, whereas the treatment groups ranged from 15.91 +/-3.87 to 17.54 +/- 3.51 pg/ml (Table 2). The TNF-alpha model group expressed 27.43 +/- 6.48 pg/ml, whereas the treatment group ranged from 14.46 +/- 3.26 to 16.22 +/- 3.54 pg/ml (Table 2). Embodiments that did not contain turmeric had a suboptimal effect in treating inflammation (¶ 129). The compositions were administered daily (¶ 116).
She does not teach a lipid mulitiparticulate, nor an explicit embodiment as claimed with the expression level reduction of claims 21 and 22.
Hingorani teaches stable solid lipid particle compositions for improved bioavailability of lipophilic compounds for age-related diseases, including osteoarthritis (abs, ¶¶ 7, 54). The compositions comprise a plurality of solid lipid microparticles containing an active ingredient in their core or embedded in the solid lipid microparticles (¶ 51). As evidenced by Westeson, solid lipid particles comprising a lipid matrix (abs, col 6 2nd ¶). Curcumin, a turmeric extract, is a potent antioxidant and anti-inflammatory agent acting on pro-inflammatory mediators including COX-2, iNOS, il-I and TNFα (¶¶ 4, 5). Boswellic acids (Boswellia serrata) have anti-inflammatory properties and are traditionally used for the treatment of osteoarthritis (¶ 183). Curcumin as a turmeric extract and boswellic acid were known to have poor bioavailability, stability, solubility, and permeability of the active in the gut (¶¶ 12, 183). The lipid microparticles comprise about 15-40% of at least one active compound (¶ 46, claim 22). The boswellic acid embodiments caused a marked lowering of IL-2 and LL-4 levels compared to baseline and was effective in modulating inflammatory cytokines (¶¶ 185-189). The lipid particles may be formulated into any suitable oral nutraceutical or pharmaceutical dosage forms including, but not limited to, tablets, capsules, powders, liquids, etc. (¶ 89). In embodiments, the formulations contained 100 mg of 40% boswellic acid (¶ 185).
She and Hingorani are discussed above and purely arguendo, if somehow the particles made obvious above not read on the lipid multiparticulates as claimed, the following applies.
Diorio teaches lipid multiparticulate formulations comprising at least one active agent (abs). Lipid multiparticulates are advantageous active agent forms because they are amenable for use in scaling dosage forms according to the weight of an individual animal, including humans, in need of treatment by simply scaling the mass of particles in the dosage form to comport with the animal's weight (¶ 38). They allow the incorporation of a large quantity of active (¶ 38). Multiparticulates also have numerous therapeutic advantages over other dosage forms, especially when taken orally, including (1) improved dispersal in the gastrointestinal (GI) tract, (2) relatively rapid and reproducible passage from the stomach, (3) more uniform GI tract transit time, and (4) reduced inter- and intra-patient variability (¶ 38). The lipid multiparticulates comprise a lipid matrix (¶¶ 4, 8, 37). A molten mixture is formed by sufficiently mixing the active agent and other components (¶ 51). The active agent may be extracted from a natural product (¶ 21). The lipid multiparticulates comprise from 1-60 wt% of the active agent (¶ 40, claim 5). The particles may be compressed into tablets (¶ 55).
Regarding claim 1, it would have been obvious to formulate a composition comprising an extract of turmeric and undenatured type II collagen, where the combination was known to have improved effect in arthritis and inflammatory-related disease, and where the combination was capable of reducing expression levels of IL-1beta and TNF-alpha.
Regarding the lipid multiarticulate of claim 1, where Hingorani teaches curcumin as an extract of turmeric and boswellic acids were known to have improved bioavailability in lipid particles, it would have been obvious to formulate the particles of She in known lipid particle forms suitable for active agent delivery, including the lipid multiparticulates of Diorio. The skilled artisan would have been motivated where Diorio teaches the lipid multiparticulates have several advantages over other dosage forms, including (1) improved dispersal in the gastrointestinal (GI) tract, (2) relatively rapid and reproducible passage from the stomach, (3) more uniform GI tract transit time, and (4) reduced inter- and intra-patient variability, and can be adjusted for the weight of the subject, etc. Further, where the components that are not the active agent make up the matrix, and the active agent is mixed with the molten matrix components prior to forming into the lipid multiparticulates, it would have been obvious to distribute the active agent throughout the lipid matrix, as suggested by Diorio.
Regarding claim 2, where the composition made obvious above comprises the active agent distributed in the lipid matrix of the lipid multiarticulate, it appears the active agent is encapsulated by the lipid matrix.
Regarding claim 3, where Diorio teaches the lipid microparticles comprise 1-60 wt% of the active agent, and where Hingorani teaches turmeric, curcumin as an extract of turmeric, and boswellic acids were known to be included in lipid particles in an amount of about 15-45% of the at least one active compound, wherein the active compounds may be selected from curcumin as a turmeric extract, it would have been obvious to include the active in the lipid multiarticulate in an amount of 1-60 wt% of the particles, falling within the claimed range.
Regarding claim 4, it would have been obvious to formulate the composition in the form of a tablet, as taught by She. Further, the skilled artisan would have had a reasonable expectation of success in formulating the lipid multiparticulates in a tablet where the lipid particles of Diorio are taught to be suitable for tablet formulations.
Regarding claim 5, it would have been obvious to formulate the composition made obvious above with undenatured type II collagen in amounts from the working examples of She, such as 61.72 mg undenatured type II collagen ((50 g/1215 g) x 1.5 g = 61.72 mg/tablet) from example 4, falling within the claimed range.
Regarding claim 6, it would have been obvious to formulate the composition made obvious above with an amount of curcumin as an extract of turmeric from the working examples of She, such as 12.35 mg undenatured type II collagen ((10 g/1215 g) x 1.5 g = 12.35 mg/tablet) from example 4, falling within the claimed range.
Regarding claim 7, where undenatured type II collagen is made obvious above, the limitation is met.
Regarding claim 8, the composition made obvious above comprises a turmeric extract, thereby meeting the claimed limitation.
Regarding claim 14, it would have been obvious to administer a therapeutically effective amount of the composition made obvious above to improve joint pain or inflammation, where She and Hingorani are both directed to compositions for treating osteoarthritis by administering anti-inflammatory agents to a subject.
Regarding claim 15, where the She teaches the combination of turmeric and type II collagen decreased expression levels of IL-1beta from 28.26 +/- 6.29 pg/mL in the model group to 15.91 +/-3.87 to 17.54 +/- 3.51 pg/ml for the treatment groups, and decreased expression levels of TNF-alpha from 27.43 +/- 6.48 pg/ml in the model group to 14.46 +/- 3.26 to 16.22 +/- 3.54 pg/ml for the treatment groups, the decrease in IL-1beta was up to about 33.8% and the decrease in TNF-alpha was up to about 33%, the ranges overlapping those instantly claimed.
Regarding claim 17, where undenatured type II collagen is made obvious above, the limitation is met.
Regarding claim 18, were an extract of turmeric is made obvious above, the claimed limitations are met.
Regarding claim 20, where She teaches administration of the composition results in an improvement in inflammation, as evidenced by the reduction in IL-1beta and TNF-alpha expression levels after two weeks of treatment, the skilled artisan would reasonably expect that at least some improvement in inflammation would occur within the first week, where the collagen and turmeric were known anti-inflammatory agents. Purely arguendo, if not, it would have been obvious for the skilled artisan to have routinely optimized the duration of treatment, amount of collagen and active agent, depending on the desired anti-inflammatory or pain reduction effects for desired treatments and severity of the condition to be treated. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2144.05(II)(A).
Regarding claim 21, where She teaches administration of the composition results in an improvement in inflammation, as evidenced by the reduction in IL-1beta and TNF-alpha expression levels after two weeks of treatment of up to 33.8% and 33% respectively, it would have been well within the relative skills of the skilled artisan to have routinely optimized the duration of treatment, amount of collagen and active agent, depending on the desired anti-inflammatory marker reduction or pain reduction effects for desired treatments and severity of the condition to be treated. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2144.05(II)(A).
Regarding claim 22, where the composition of the method made obvious above showed a decrease in serum IL-1beta of 33.8%, it appears that the limitation of a reduction in interleukin-1 of at least about 20% is met. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding claim 26, it would have been obvious to administer the composition made obvious above daily, as taught by She.
Claims 9, 10, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over She (CN 109010805 A, cited on IDS dated 07/29/2024), Hingorani et al (US 20170333362 A1, hereinafter “Hingorani”), and Diorio et al (US 20170354599 A1, hereinafter “Diorio”), as applied to claims 1-8, 14-18, 20-22, 25, and 26 above, and further in view of Wang et al (Osteoarthritis and Cartilage, 2014, vol 22, issue 1, pp. 128-132, hereinafter “Wang”).
She, Hingorani, and Diorio are discussed above, and while Hingorani teaches boswellic acid modulates inflammatory cytokines with a reduction in IL-2 and IL-4, and IL-1 and TNF-alpha were tested, the reference does not explicitly state a reduction in the expression levels of those instantly claimed.
Wang teaches boswellic acid, especially acetyl-11-keto-beta-boswellic acid, attenuates osteoarthritis, has anti-inflammatory effects, and suppresses production; of IL-1 beta, TNF-alpha, etc. (abs, pg. 129 1st col 1st ¶, fig. 2).
Regarding claims 9 and 19, it would have been obvious to modify the composition and method made obvious above by selecting from other known anti-inflammatory active agents that were known to modulate inflammatory cytokines for osteoarthritis, such as boswellic acid (Boswellia serrata), as taught by Hingorani, and where boswellic acid was known to specifically reduce IL-1 beta and TNF-alpha expression levels in osteoarthritis, as taught by Wang. The skilled artisan would have had a reasonable expectation of success where She, Hingorani, and Wang are all directed to composition capable of reducing inflammation in joints.
Regarding claim 10, it would have been obvious to include boswellic acid comprising acetyl-11-keto-beta-boswellic acid, in known amount suitable for anti-inflammatory compositions capable of treating osteoarthritis, such as 40 mg, as taught by Hingorani, falling within the claimed range.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over She (CN 109010805 A, cited on IDS dated 07/29/2024), Hingorani et al (US 20170333362 A1, hereinafter “Hingorani”), and Diorio et al (US 20170354599 A1, hereinafter “Diorio”), as applied to claim 1-8, 14-18, 20-22, 25, and 26 above, and further in view of Mannelli et al (BMC Musculoskelet Discord, 2013, 14:228, pp. 1-9, hereinafter “Mannelli”).
She, Hingorani, and Diorio are discussed above but do not specifically teach the mg/kg of collagen per day.
Mannelli teaches type II collagen was known to be administered at 1, 3, and 10 mg/kg to relieve and prevent pain in osteoarthritis (abs).
It would have bene obvious to modify the method made obvious above by including known concentrations of collagen suitable for reducing pain in osteoarthritis, such as 1 or 3 mg/kg, where the composition made obvious above and Mannelli are directed to improving pain or inflammation in osteoarthritis. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over She (CN 109010805 A, cited on IDS dated 07/29/2024), Hingorani et al (US 20170333362 A1, hereinafter “Hingorani”), and Diorio et al (US 20170354599 A1, hereinafter “Diorio”), as applied to claim 1-8, 14-18, 20-22, 25, and 26 above, and further in view of Acharya et al (WO 2021111312 A1, hereinafter “Archarya”).
She, Hingorani, and Diorio are discussed above but do not teach a Kellgren-Lawrence score specifically.
Acharya teaches stable curcumin compositions for prevention and maintenance of arthritis and osteoarthritis, wherein the curcumin is an extract from Curcuma longa (abs, pg 1 ln 19-20). Administration of curcumin was known to decrease the Kellgren-Lawrence score in osteoarthritis, with a reduction of greater than 20% for both 100 mg/kg and 200 mg/kg curcumin administration (fig. 7B).
Where the composition made obvious above is directed to decreasing inflammation or pain associated osteoarthritis, and the combination of collagen and turmeric and/or curcumin as an extract of turmeric was known to reduce inflammation, it would have been obvious to formulate the composition made obvious above in a sufficient amount suitable to decrease the Kellgren-Lawrence score of greater than 20%, where curcumin as an extract of Curcuma long was known to cause reductions in Kellgren-Lawrence scores falling within the claimed range. Further, it would have been well within the relative skilled of the skilled artisan to have routinely optimize the amount of the composition, the concentration of the active agent, etc., in order to achieve desired reduction in Kellgren-Lawrence score. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2144.05(II)(A).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-10, 14-22, and 25-27, are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 18/834,006 (reference application), hereinafter ‘006, in view of She (CN 109010805 A, cited on IDS dated 07/29/2024), Diorio et al (US 20170354599 A1, hereinafter “Diorio”), Wang et al (Osteoarthritis and Cartilage, 2014, vol 22, issue 1, pp. 128-132, hereinafter “Wang”), Mannelli et al (BMC Musculoskelet Discord, 2013, 14:228, pp. 1-9, hereinafter “Mannelli”), Acharya et al (WO 2021111312 A1, hereinafter “Archarya”), and Li et al (Inflammation, 2017. vol 5, no 5, pp. 1599-1605, hereinafter “Li”). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims disclose lipid multiparticulate particles comprising an anti-inflammatory active agent for joint health, including boswellic acid from Boswellia derived compound. The active agent is present in the particles from about 1-80 wt%. The active agent is present from about 1-1000 mg. The collagen comprises undenatured collagen. Also disclosed is method of reducing inflammation in a mammal. The active agent is encapsulated in the lipid matrix.
The claims of ‘006 do not disclose the dosage forms of claim 4, the amount of collagen, wherein collagen is Type II collagen, the percent decrease in the markers claimed, the per day dose of collagen, a Kellgren-Lawrence score, daily administration, nor the extracts/and or isolates of claims 27 and 28.
It would have been obvious to formulate the compositions of ‘006 in tablet form, which were known to be suitable for anti-inflammatory compositions comprising boswellic acid, as taught by She, and where Diorio teaches lipid multiparticulates were known to be tableted.
It would have been obvious to use known collagen suitable for anti-inflammatory composition, including undenatured type II collagen, as taught by She.
It would have been obvious to use known amounts of collagen suitable for anti-inflammatory compositions, such as those taught by She and Mannelli for the same reasons above.
Regarding the decrease in the serum levels, where boswellic acid is disclosed as an anti-inflammatory agent, where Wang teaches boswellic acid was known to decrease serum levels of those instantly claimed, and where She teaches collagen in combination with an anti-inflammatory agent resulted in a significant decrease in serum levels, it would have been obvious to formulate the composition for a decrease in serum levels as instantly claimed, depending on the desired condition to be treated, severity of the condition, etc.
Where the compositions are directed to anti-inflammatory compositions, depending on the desired use, it would have been obvious to formulate the composition for lowering a Kellgran-Lawrence score of 20%, where this was known from Archarya.
It would have been obvious to administer the composition daily, which was known from She, depending on the desired use of the composition.
It would have been obvious to select from other known active agent suitable for anti-inflammatory compositions, such as andrographolide from Andrographis paniculate, as taught by Li.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-10, 14-22, and 25-27, are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 18/833,990 (reference application), hereinafter ‘990, in view of She (CN 109010805 A, cited on IDS dated 07/29/2024) and Mannelli et al (BMC Musculoskelet Discord, 2013, 14:228, pp. 1-9, hereinafter “Mannelli”). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims disclose a joint health composition and methods thereof for improving one or more of joint health and inflammation comprising lipid multiparticulate particles and an anti-inflammatory compound, wherein the anti-inflammatory agent compound comprises an extract or isolate from those instantly claimed. The anti-inflammatory compound is about 1 mg to about 1000 mg. The anti-inflammatory compound is present in the particles in an amount from about 1-80 wt%. The active agent is encapsulated in the lipid matrix. The form may be a tablet, capsule, etc. The decrease in serum levels appear to be the same as those instantly claimed. The composition is administered in an amount sufficient to change a Kellgran-Lawrence score by at least 20%. The composition is administered daily.
The claims of ‘990 do not disclose collagen.
It would have been obvious to include collagen, where collagen was known to improve the reduction in serum levels of TNF-alpha and IL-1 beta when used in combination with an anti-inflammatory compound, as taught by She.
It would have been obvious to use known collagen suitable for anti-inflammatory composition, including undenatured type II collagen, as taught by She.
It would have been obvious to use known amounts of collagen suitable for anti-inflammatory compositions, such as those taught by She and Mannelli for the same reasons above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/JOSHUA A ATKINSON/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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