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 .
DETAILED ACTION
Claim Status
This action is in response to the claims filed on 11/05/2024.
Claims 1-11 are pending and are considered on the merits.
Priority
This application is a 371 of PCT/KR2022/013880 (filed on 09/16/2022), which claims benefit from foreign applications KR10-2021-0124425 (filed on 09/17/2021). The priority claim of the instant application has been granted and the earliest benefit date is 09/17/2021 from the application KR10-2021-0124425.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/15/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. The corresponding signed and initialed PTO form 1449 has been mailed with this action.
Claim Objections
Claim 6 is objected to because of the following informalities:
Claim 6 recites the phrase “treating cartilage injury disease”. It is recommended to change to “treating a cartilage injury disease”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 9 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 9 contains the trademark/trade name “thermogel”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name “thermogel” is used to identify/describe a material which undergoes a sol-to-gel transition in response to heat to form a gel. Accordingly, the identification/description is indefinite.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-2 and 5 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. The claims recite a composition containing an antifolate, which is not markedly different from its naturally occurring counterpart. This judicial exception is not integrated into a practical application because the natural product is not linked to a particular technology. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements merely describe the characteristics of the product of nature.
Applicant is directed to the 2019 Revised Patent Subject Matter Eligibility Guidance published in the Federal Register (84 FR 50) on 1/07/2019, which is found at: https://www.govinfo.gov/content/pkg/FR-2019-01-07/pdf/2018-28282.pdf; and the October 2019 Update: Subject Matter Eligibility, which is found at https://www.uspto.gov/sites/default/files/documents/peg_oct_2019_update.pdf.
Briefly summarized here, the new guidance cites a two part test: is the claimed invention directed to a statutory class of invention (Step 1), if so then is the claimed invention as a whole directed to a law of nature, natural phenomena, or an abstract idea (i.e. set forth or described in the claim) (Step 2A, prong one), if so then is the claimed invention recite additional elements that integrate the judicial exception into a practical application (Step 2A, prong two), if not then does the claim as a whole amount to significantly more than the judicial exception (Step 2B).
In regard to Step 1, claims 1-2 and 5 are drawn to a composition of matter – a composition containing an antifolate.
In regard to Step 2A prong one, claims 1-2 and 5 are drawn to a nature-based product which is not markedly different from its naturally occurring counterpart. Specifically, claims 1-2 and 5 are drawn to a composition containing an antifolate. It is noted that the limitation “for inducing differentiation of stem cells into chondrocytes" in instant claims 1-2 and 5 is interpreted as intended use. See MPEP 2111.02 II. Thus, instant claims 1-2 and 5 are reasonably interpreted as a composition containing an antifolate, within the concentration range in claim 5, that is capable of performing the intended use for inducing differentiation of stem cells, selected from the list in claim 2, into chondrocytes. Since instant claims 1-2 and 5 recite only one component, i.e., an antifolate, in the claimed composition for the intended use, it is clear that the antifolate would be sufficient to perform the claimed intended use.
Applicant is directed to the prior art Fu et al., (Nature Communications. 2017; 8: 1529, p. 1-9). Fu teaches the natural product carolacton is a macrolide keto-carboxylic acid produced by the myxobacterium Sorangium cellulosum, and inhibits folate-dependent C1 metabolism (e.g., abstract). Fu teaches it is possible to use carolacton as an inhibitor tool compound to assess MTHFD2 as an anticancer target (e.g., abstract). Thus, Fu teaches a natural product that inhibits folate-dependent metabolism and can be used as a medicine. It is noted that the specification defines the term “antifolate” as “antifolates are a class of antimetabolite medications that antagonize the actions of folic acid” ([0003]). Thus, instant claims encompass a composition containing an antifolate that is identical (no difference in structural or functional characteristics) to the natural product carolacton taught by Fu. Because there is no difference between the claimed and naturally occurring antifolate, the claimed composition containing an antifolate does not have markedly different characteristics, and thus is a “product of nature” exception. Accordingly, instant claims are directed to a judicial exception.
In regard to Step 2A prong two, the judicial exception is not integrated into a practical application. In particular, it is noted that claim 2 recites a list of stem cells directed to the intended use limitation in claim 1, and claim 5 merely recites a concentration range of the antifolate. Thus, claims 1-2 and 5 recite no additional elements to integrate the claimed composition containing an antifolate into a practical application. Moreover, these elements merely describe the characteristics of the product of nature, e.g. intended use or concentration, without any modifications, and there is no inventive concept to improve a technology, affect a particular treatment, or implement with a particular device to provide a meaningful limitation on the judicial exception.
In regard to Step 2B, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. As stated supra, claims 1-2 and 5 recite no additional elements to integrate the claimed composition containing an antifolate into a practical application. The elements recited in claims 2 and 5 merely describe the characteristics of the product of nature, as discussed above, there is no inventive concept provided.
Therefore, claims 1-2 and 5 are directed to a natural antifolate in a composition, that is not markedly different from its naturally occurring counterpart, is not integrated into a practical application, and does not include elements that amount to significantly more than the natural product itself and do not qualify as patent eligible subject matter under 35 U.S.C. § 101.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-2 and 5 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Fu et al., (Nature Communications. 2017; 8: 1529, p. 1-9).
With respect to claims 1-2 and 5, as stated supra, it is noted that the specification defines the term “antifolate” as “antifolates are a class of antimetabolite medications that antagonize the actions of folic acid” ([0003]). It is also noted that the limitation “for inducing differentiation of stem cells into chondrocytes" in instant claims 1-2 and 5 is interpreted as intended use. MPEP 2111.02 II states “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention' s limitations, then the preamble is not considered a limitation and is of no significance to claim construction”. Thus, instant claims 1-2 and 5 are reasonably interpreted as a composition containing an antifolate, within the concentration range in claim 5, that is capable of performing the intended use for inducing differentiation of stem cells, selected from the list in claim 2, into chondrocytes.
Fu teaches a natural product carolacton inhibits folate-dependent C1 metabolism (e.g., abstract). Fu teaches it is possible to use carolacton as an inhibitor tool compound to assess MTHFD2 as an anticancer target (e.g., abstract). Thus, Fu teaches a composition containing a natural product carolacton that inhibits folate-dependent metabolism and can be used as a medicine, i.e., a composition containing an antifolate as claimed in claims 1 and 2. Fu tests carolacton at the concentrations of 200 nM (0.2 µM), 100 nM (0.1 µM) and 50 nM (0.05 µM) (see e.g., Fig 2b), within the claimed range in claim 5. Since Fu teaches the same product as that in claims 1, 2 and 5, and since MPEP 2112.01(II) states that "products of identical chemical composition cannot have mutually exclusive properties. A chemical composition and its properties are inseparable.", the product of Fu would have been capable of performing the intended use for inducing differentiation of stem cells, cited in claim 2, into chondrocytes as cited in claim 1.
Accordingly, Fu anticipates instant claims.
Claims 1-2 and 5-7 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Zhai et al., (Stem Cells Int. 2021 Jan 9:2021:8850820, p. 1-15. Cited in IDS 03/15/2024).
With respect to claim 1, it is noted that the limitation “for inducing differentiation of stem cells into chondrocytes" is interpreted as intended use. See MPEP 2111.02 II. Thus, claim 1 is reasonably interpreted as a composition containing an antifolate that is capable of performing the intended use “for inducing differentiation of stem cells into chondrocytes”.
Zhai teaches combined application of mesenchymal stem cells (MSCs) and methotrexate (MTX) increased the therapeutic effects on rheumatoid arthritis (RA) (e.g., title and abstract). Zhai teaches coculture of mesenchymal stem cells (UCs, standing for MSCs isolated from umbilical cords) with MTX in a basal medium or in an osteogenic differentiation medium (see e.g., p. 3, left col, para 2.6 “MTT assay” and p. 3, right col, Results section, para 3.1. “Isolation and Characterization of MSCs with or without MTX Treatment”), thus teaches a composition (a basal medium or an osteogenic differentiation medium) containing an antifolate (methotrexate, “MTX”). Zhai teaches the Alizarin red staining (Figure S1b) showed that mineralized nodules formation of UCs could be induced when treated with MTX (p. 3, right col, Results section, para 3.1, and see p. 13, Fig S1b), thus teaches the composition containing the antifolate methotrexate is capable of inducing differentiation of stem cells into chondrocytes.
With respect to claim 2, as stated supra, Zhai teaches the mesenchymal stem cells (MSCs) are obtained from human umbilical cords (e.g., p. 2, right col, para 2.2 “Cell Culture”).
With respect to claim 5, as stated supra, Zhai teaches coculture of MSCs with different MTX concentrations (0, 1, 10, and 100 μg/mL) in a basal medium (see e.g., p. 3, left col, para 2.6 “MTT assay”), thus teaches a concentration of the antifolate being 0 μM, 2.2 μM, 22 μM, and 220 μM, in which the concentrations of 2.2 μM and 22 μM MTX are within the claimed range.
With respect to claim 6, similarly, it is noted that the limitation “pharmaceutical” and the limitation “for treating a cartilage injury disease" are interpreted as intended use. See MPEP 2111.02 II. Thus, claim 6 is reasonably interpreted as a composition containing an antifolate and stem cells that is capable of performing the intended “pharmaceutical” use “for treating a cartilage injury disease”.
Zhai teaches coculture of mesenchymal stem cells with MTX in a basal medium (see e.g., p. 3, left col, para 2.6 “MTT assay”), thus teaches a composition (a basal medium) containing an antifolate (methotrexate, “MTX”) and stem cells (mesenchymal stem cells). Zhai teaches combined application of mesenchymal stem cells (MSCs) and methotrexate (MTX) increased the therapeutic effects on rheumatoid arthritis (RA) (e.g., title and abstract, see Figure 1), thus teaches the composition containing the antifolate and the stem cells is capable of performing a pharmaceutical use for treating a cartilage injury disease, such as rheumatoid arthritis.
With respect to claim 7 directed to the disease being rheumatoid arthritis, as stated supra, Zhai teaches the composition is capable of treating a cartilage injury disease, such as rheumatoid arthritis (e.g., abstract, see Figure 1).
Accordingly, Zhai anticipates instant claims.
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 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over Zhai et al., (Stem Cells Int. 2021 Jan 9:2021:8850820, p. 1-15. Cited in IDS 03/15/2024) in view of Visentin et al., (Hematol Oncol Clin North Am. 2012; 26(3): 629-648, PubMed version, p. 1-23).
Claims 1-2 and 5-7 are anticipated by Zhai. Thus, Zhai makes obvious claims 1-2 and 5-7.
Claims 3-4 are directed to the antifolate being pralatrexate.
However, Zhai uses methotrexate (MTX) but is silent on pralatrexate.
Nonetheless, Zhai teaches “MTX is a structural analogue of folic acid and blocks cell growth and reproduction via inhibiting dihydrofolate reductase [26]” (see p. 7, left col, last para. It is noted that reference [26] is Visentin et al., cited herein).
Visentin summarizes the antifolates (see e.g., title and abstract). Visentin teaches based on the understanding of MTX, “a search was undertaken to create a structural analog that would enhance its activity and its selectivity….This led to the development of pralatrexate”, and “This drug has a much higher affinity for reduced folate carrier (RFC) and folylpolyglutamate synthetase (FPGS) than methotrexate (MTX)” and “Pralatrexate does appear to have enhanced “selectivity”” (p. 6, last para “The Emergence of a New-Generation 4-amino-antifolate – Pralatrexate” to p. 7, para 1-2). Thus, Visentin teaches pralatrexate is a new generation antifolate that has enhanced activity and selectivity than methotrexate.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the composition containing an antifolate methotrexate that is capable of inducing differentiation of stem cells into chondrocytes disclosed by Zhai, by substituting pralatrexate for methotrexate as suggested by Visentin with a reasonable expectation of success. Since Visentin teaches pralatrexate is a new generation antifolate that has enhanced activity and selectivity than methotrexate (see above), one of ordinary skill in the art would have had a reason to substitute pralatrexate for methotrexate as suggested by Visentin in order to test the therapeutic effect of the new generation antifolate that has enhanced activity and selectivity than methotrexate.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Claims 1-2 and 5-11 are rejected under 35 U.S.C. 103 as being unpatentable over Zhai et al., (Stem Cells Int. 2021 Jan 9:2021:8850820, p. 1-15. Cited in IDS 03/15/2024) in view of Park et al., (Macromol. Biosci. 2015, 15, 464-472. Cited in IDS 03/15/2024).
Claims 1-2 and 5-7 are anticipated by Zhai. Thus, Zhai makes obvious claims 1-2 and 5-7.
Claim 8 is directed to a sustained-release dosage form comprising the composition of claim 1. Claim 9 is directed to the sustained-release dosage form being a thermogel. Claim 10 is directed to the form comprising a PEG-poly(L-alanine) copolymer. Claim 11 is directed to the form further comprising stem cells.
As stated supra, Zhai teaches a composition containing the antifolate methotrexate that is capable of inducing differentiation of stem cells into chondrocytes. Zhai teaches the composition further comprises stem cells (i.e., mesenchymal stem cells, see e.g., p. 3, left col, para 2.6 and right col, para 3.1), related to claim 11.
However, Zhai is silent on a sustained-release dosage form in claim 8, a thermogel in claim 9, or a PEG-poly(L-alanine) copolymer in claim 10.
Park teaches a PEG-Poly(l-alanine) thermogel as a 3D scaffold of bone-marrow-derived mesenchymal stem cells (see e.g., title and abstract), thus teaches a thermogel in claim 9, a PEG-poly(L-alanine) copolymer in claim 10, and the composition further comprising stem cells in claim 11. Since both the instant claims 9 and 10 disclose the thermogel and the PEG-poly(L-alanine) copolymer are a sustained-release dosage form, one of ordinary skill in the art would have immediately expected that the PEG-Poly(l-alanine) thermogel of Park is a sustained-release dosage form in claim 8. Park teaches the PEG-PA thermogel is a very promising as a 3D culture matrix as well as an injectable tissue-engineering system for preferential chondrogenic differentiation of the BMSCs (see e.g., abstract and see Figs 4-5), related to claim 8.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the composition containing an antifolate methotrexate that is capable of inducing differentiation of stem cells into chondrocytes disclosed by Zhai, by combining a PEG-poly(L-alanine) copolymer thermogel so as to obtain a sustained-release dosage form as suggested by Park with reasonable expectation of success. Since Park teaches the PEG-PA thermogel is a very promising 3D culture matrix as well as an injectable tissue-engineering system for preferential chondrogenic differentiation of the BMSCs (see e.g., abstract) and since Zhai aims to test the therapeutic effects on rheumatoid arthritis by combined application of MSCs and methotrexate (e.g., abstract), one of ordinary skill in the art would have had a reason to combine a PEG-poly(L-alanine) copolymer thermogel as suggested by Park to encapsulate the mesenchymal stem cells and methotrexate of Zhai in order to perform a combined application of the MSCs and methotrexate to test the therapeutic effects on rheumatoid arthritis.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Double Patenting Rejections
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-2 are rejected on the ground of nonstatutory double patenting as being unpatentable over patented claims in US Patent Nos: 12,043,594 (‘594), 6,201,072 (‘072), and 6,117,949 (‘949). Although the claims at issue are not identical, they are not patentably distinct from each other.
It is noted that the limitation “for inducing differentiation of stem cells into chondrocytes" in instant claims 1-2 is interpreted as intended use. See MPEP 2111.02 II. Thus, instant claims 1-2 are reasonably interpreted as a composition containing an antifolate that is capable of performing the intended use for inducing differentiation of stem cells, selected from the list in claim 2, into chondrocytes. Since instant claims 1-2 recite only one component, i.e., an antifolate, in the claimed composition for the intended use, it is clear that a composition containing an antifolate would be sufficient to perform the claimed intended use.
Regarding a composition containing an antifolate, claims in US Patents ‘594, ‘072 and ‘949 recite a composition comprising methotrexate (MTX) (‘594 claim 7), an aqueous polymeric composition comprising methotrexate (‘072 claim 24 and ‘949 claim 22), thus recite a composition containing an antifolate (i.e., methotrexate).
The difference between the cited patent claims and the instant claims lies in the fact that the cited patent claims are much more specific. Thus the invention of said claims of the cited patent are in effect “species” of the “generic” invention of the instant claims. It has been held that the generic invention is “anticipated” by the “species”. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993).
Since the instant application claims are anticipated by cited patent claims, said claims are not patentably distinct.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jianjian Zhu whose telephone number is (571)272-0956. The examiner can normally be reached M - F 8:30AM - 4PM (EST).
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/JIANJIAN ZHU/Examiner, Art Unit 1631
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