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
This action is in response to papers filed on May 31st 2024. Claims 1-15 have been canceled and claims 16-24 are newly added by Applicants’ amendment filed on 5/31/2024. It is noted that both claims 16 and 21 are independent claims.
Therefore, claims 16-24 are under examination to which the following grounds of rejection are applicable.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application PCT/JP2022/043735 filed on November 28, 2022.
Applicant’s claim for the benefit of a prior-filed parent US Provisional Application 63/284,638 filed December 1, 2021 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Receipt is acknowledged of certified untranslated copies of papers required by 37 CFR 1.55.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Therefore, the earliest possible priority date for the instant application is December 1, 2021.
Specification
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim objection
Claims 16, 17, 18, 21 and 22 are objected to because of the following informalities: abbreviations such as Hap should be spelled out at the first encounter in the claims. Appropriate correction is required.
Claim 16 is missing the indefinite article “a” before “biocompatible resin” in line 6. The term should be amended to recite “a biocompatible resin”. Appropriate correction is required.
Claim 21 is missing the indefinite article “an” before “containing adhesive protein” in line 10. The term should be amended to recite “containing an adhesive protein” . 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.
Claims 16-24 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 claim 16 and 21, it is indefinite in its recitation of the phrase “predetermined number of mesenchymal stem cells “ and “predetermined time period” as the claim does not define the number or range of cells, and/or the length of the time period that the mesenchymal stem cells are captured in.
Further, claims 16 and 21 are rendered indefinite in its recitation of the term “uneven structure” in line 7 and 5 respectively. The term “uneven” is a relative term which renders the claim indefinite. The term “uneven” 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. As such, the metes and bounds of this claim are rendered indefinite.
Claim 16 and 21 are rendered indefinite for its recitation of the term “partially exposed” in line 8 and 6, respectively. The term “partially” is a relative term which renders the claim indefinite. The term “partially” 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. Furthermore, it is unclear what the fibers are exposed to (i.e. culture medium), as the description is not provided in the claims. As such, the metes and bounds of this claim are rendered indefinite.
Moreover, claims 16 and 21 is rendered indefinite for its recitation of the term “the microenvironment” in line 22 and 18 respectively. There is insufficient antecedent basis for this limitation in the claim.
Further, claims 16 and 21 are indefinite in its recitation of the terms “plurality of fibers”, “fiber length” and “fiber diameter” as it is unclear if the “fiber(s)” are drawn to the biocompatible fibers recited in the claim, or they refer to a completely different property. There is insufficient antecedent basis for this limitation in the claim.
Claims 16 and 21 are indefinite in their recitation of “ a non-woven mat formed of biocompatible fibers” as it is unclear whether a non-woven mat comprises biocompatible fibers or has been produced by biocompatible fibers that are not necessary present in the claimed non-woven mat. As such the metes and bounds of the claim are indefinite.
Claim 17 is indefinite because of its recitation of “the adhesive protein”. Claim 17 depends on claim 16 which recites “adhesive proteins”. There is not proper antecedent bases for “adhesive protein” in claim 17.
Claim 19 is indefinite because of its recitation of “containing an adhesive protein”. Claim 19 depends on claim 16 which recites “adhesive proteins”. There is not proper antecedent bases for “adhesive protein” in claim 19.
Claim 21 is a product claim directed to a non-woven mat. The claim also recites the following steps “ by immersing the non-woven mat in a medium” and “by seeding a cell suspension containing a predetermined number of mesenchymal stem cells on the non-woven mat in the cell culturing container”. It is unclear if the claimed method steps are adding any structural limitation ot the product claim. In other words claim 21 is indefinite for the recitation of both a product and the method steps of using the product in a single claim (See; MPEP 2173.05(p); and IPXL Holdings v. Amazon.com, Inc., 430 F.2d 1377, 1384, 77 USPQ2d 1140, 1145 (Fed. Cir. 2005); Ex parteLyell, 17 USPQ2d 1548 (Bd. Pat. App. & Inter. 1990) (claim directed to an automatic transmission workstand and the method of using it held ambiguous and properly rejected under 35 U.S.C. 112, second paragraph).
Claims 20 and 24 are indefinite in their recitation of “the thickness” . There is not proper antecedent bases in the claims.
Claim 21 is indefinite in its recitation of “the cell culture container” in line 14. There is not proper antecedent bases for of “the cell culture container” in the claim.
Claim 21 recites “a medium containing adhesive protein, adhesive proteins contained in the medium” in lines 10-11, rendering the claim unclear.
Claims 18 and 22-23 are rejected insofar that they depend on claims 16 and 21 respectively.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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(s) 16, 18, 20-22, and 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sunami et al. (Published: 2019. WIPO Patent Publication: WO 2019168000 A1 Filed in IDS 6/24/2024, Cite No 1), in view of Zandi et al. (Published: 2010. J. Biomed. Mater. Res., 92A: 1244-1255).
The applied Sunami et al. reference has a common applicant with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(1). The publication dated for Sunami et al. is September 6, 2019. The earliest effective filing date of the instant application is December 1, 2021.
Therefore rejection under 35 U.S.C. 103 CANNOT be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02. Because the reference qualifies as prior art under 102(a)(1), the provisions of MPEP 717.02 do not apply.
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Regarding claim 16 and 21, Sunami teaches a method and a non-woven mat for culturing stem cells within a non-woven sheet (para 0011, "A mass of adipose tissue containing adipose-derived stem cells collected from the patient's body is placed in a culture vessel, and a nonwoven sheet made of biodegradable fibers with an outer diameter of 10μm or more and 100μm or less with gaps between fibers of 10μm to 500μm is placed on the fat tissue mass… thereby causing the crawling adipose-derived stem cells to proliferate massively in the gap spaces between fibers of the nonwoven fabric sheet”), the method comprising: immersing the non-woven mat formed of fibers in a medium filled in a culturing container (Abstract, “By immersing the nonwoven fabric as such in a culture medium, a number of adipose-derived stem cells are allowed to crawl out from the adipose tissue and then adhered to the fiber surface; para 0011, “By filling the container with medium for adipose-derived stem cell culture, The aforementioned mass of adipose tissue covered with the nonwoven fabric sheet is immersed in the medium for culturing fat-derived stem cells…”), wherein the biocompatible fibers contain a volume of PLGA (biocompatible resin) 50% by weight and HAp 50% (para 0054, “Composite fibers (outer diameter 10~60μm) with a composition of PLGA 50 wt% / HAp 50 wt% were spun and collected as nonwoven sheets using electrospinning, cut into 23 mm diameter circles, and used as Sample 1.”). Moreover, Sunami teaches that the non-woven mat has a plurality of fibers with a fiber diameter of 10 to 100 µm (“Since the fibers constituting the nonwoven fabric sheet of the present invention have an outer diameter of 10 to 100 μm, a sufficient space is formed between the fibers”) and that the fiber have a length (para 0028, “the fiber outer diameter is preferably about 10 to 100 μm, more preferably 30 μm to 60 μm.”). Sunami also teaches that the fibers are entangled with each other (FIG 11. See attached.)
However, Sunami fails to teach culturing of mesenchymal stem cells and they are captured within the non-woven mat, and that there are adhesive proteins contained in the medium and exposed thereon, as well as explicit lengths of fibers within the claimed range.
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Zandi teaches a hydroxyapatite (HAp) and gelatin (adhesive protein) scaffold, and assesses the biocompatibility potential of the scaffold (pp. 1244, col 1, Abstract, “This study is devoted to fabricate a novel hydroxyapatite(HAp)/gelatin scaffold coated with nano HAp in nano-rod configuration to evaluate its biocompatibility potential.”). Zandi teaches a surface of biocompatible fibers with them being partially exposed (Fig 8). Moreover, Zandi teaches that nano-HAp particles have lengths of 100-300nm (pp. 1244, Abstract, “The nano-HAp particles are needle and rod-like with widths ranging between 30 to 60 nm and lengths from 100 to 300 nm, respectively.”). Moreover, Zandi teaches that the mesenchymal stem cells are seeded into the non-woven mat, and that the cells adhered on the surface of the HAp/gelatin structure and proliferated in a microenvironment (pp. 1253 col 1, “On the basis of the SEM-micrograph, morphology of the cells adhered on the surfaces of nano-HAp/gelatin…On the basis of this assay, all the studied scaffolds exhibited an appropriate environment in which the loaded cells appeared to be proliferated during the cultivation periods”; pp 1253, col 1, “According to our findings, on day 4, the mean number of cells was about 29.3 x 10^4 cells per nano-HAp/gelatin coated with HAp, 21 x 10^4 cells per nano-HAp/gelatin and 19.1 x 10^4 cells per pure gelatin.”). Moreover, Zandi teaches that mesenchymal stem cells had better stem cell attachment and proliferation with the HAp/gelatin scaffold (pp. 1254, col 1, “The coated scaffolds seem to have a better cell attachment and proliferation.”).
It would have been obvious to modify the non-woven sheet taught by Sunami et al. comprising stem cells and select mesenchymal stem cells as taught by Zandi, as mesenchymal stem cells are known stem cell population at the time of the claimed invention. Further, a skilled artisan would have been motivated to culture mesenchymal stem cells within a non-woven sheet containing HAp particles and adhesion proteins, as Zandi teaches that mesenchymal stem cells cultured into HAp/gelatin scaffolds exhibited an appropriate environment and had improved cell proliferation.
Moreover, it would have been obvious to optimize aspects of the non-woven HAp sheet as taught by Sunami and Zandi, to have fiber lengths of fibers within the claimed range of 2mm – 80mm based on influential considerations in the design of the non-woven sheet such as gelatin concentration, processing conditions, chemical processing (pH), to achieve fiber lengths of 2mm-80mm.
The Court has stated that generally such differences amount to mere optimization and will not support patentability unless there is evidence indicating the claimed feature is critical. “[W]here 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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). In KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court held that "obvious to try" was a valid rationale for an obviousness finding, for example, when there is a "design need" or "market demand" and there are a "finite number" of solutions. 550 U.S. at 421.
MPEP § 2144 sets forth Applicant' s burden for rebuttal of a prima facie case of obviousness based upon routine optimization. Applicant must provide either a showing that the particular amount or range recited within the claims is critical; and/or a showing that the prior art reference teaches away from the claimed amount.
Regarding claim 18 and 22 , the combined teachings of Sunami and Zandi render obvious the claimed methodology of claim 16 and the claimed non-woven mat of claim 21 respectively. Moreover, Zandi teaches that the HAp particles are needle-shaped (Abstract, pp. 1245, “The nano-HAp particles are needle and rod-like with widths ranging between 30 to 60 nm and lengths from 100 to 300 nm, respectively. Because of their higher surface area and higher reactivity, the nano-rod particles were distributed in gelatin much better than spherical and mixed shapes particles”).
Regarding claims 20 and 24, the combined teachings of Sunami and Zandi render obvious the claimed methodology of claim 16, and the claimed non-woven mat of claim 21 respectively. Moreover, Sunami teaches that the non-woven mat has a thickness of 0.1 to 0.5 mm (para 0013, “Preferably, the nonwoven fabric sheet is preferably thicker than about 0.1 to 1.0 mm. If the thickness of the nonwoven fabric sheet is less than 0.1mm, stem cells can easily pass through the sheet, making it harder for them to be trapped.”).
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Claim(s) 16 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Sunami et al. (Published: 2019. WIPO Patent Publication: WO 2019168000 A1 Filed in IDS 6/24/2024, Cite No 1), in view of Zandi et al. (Published: 2010. J. Biomed. Mater. Res., 92A: 1244-1255), as applied to claim 16 above, and in further view of Chen et al. (hereinafter “Chen 2011”, Published: 2011. Nanotechnology 22 105708) and Chen et al. (hereinafter “Chen 2021”, Published: 2021. RSC Adv., 2021,11, 36360-36366).
With regard to claim 16, the combined teachings of Zandi and Sunami render obvious the claimed method, as iterated above in the 103 rejection the content of which is incorporated in claim 16.
However, the combined teachings of Zandi and Sunami fail to teach that the adhesion protein is negatively charged and that HAp particles have a positive surface charge.
Chen 2011 teaches that the hydroxyapatite particles can be positively charged, and that positively charged HAp nanoparticles show the greatest improvement for cell viability, and overall surface charge influences cell behavior (Abstract, pp.1 “…among which positively charged HAP nanoparticles showed the strongest improvement for cell viability and cell proliferation. In summary, the surface charge of HAP nanoparticles can be modified to influence the cellular uptake of HAP nanoparticles and the different uptake also influences the behavior of cells.”).
It would have been obvious for a skilled artisan to use HAp particles that are positively charged, as they have been found to improve cell viability and proliferation, displaying that varying surface charges impact cell behavior. There would have been reasonable expectations of success in combining these teachings as one of ordinary skill in the art would recognize to combine known elements in the art to give predictable results.
Chen 2011, Sunami and Zandi fail to teach that the adhesion protein has a negative effective surface charge and is adsorbed.
Chen 2021 teaches that negatively charged osteopontin (OPN) (adhesion protein) had high adsorption when exposed to a positively charged monolayer (pp. 36362, col 2, “OPN adsorbed on the SAMs with significantly different adsorption behaviours…the I-OPN count results showed that SAMs-NH2 could strongly adsorb OPN; the adsorbed amount was 89.01 ± 13.62 ng cm−2, which was 4.36-, 26.24-, 12.31- and 10.47-times the values of SAMs-OH, SAMs-OEG, SAMs-COOH and SAMs-PO3H2, respectively. This is likely to be caused by electrostatic forces between negatively charged OPN and the positively charged surface”).
It would have been obvious to modify the non-woven sheets taught by the combined teachings of Zandi, Chen 1, and Zandi, to incorporate a negatively charged adhesion protein taught by Chen 2021, as it was known at the time of the instant invention that negatively charged proteins have great electrostatic attraction to positively charged surfaces, encouraging high adsorption. A skilled artisan would reasonably expect that such application of negatively charged proteins of Chen 2021 to the positively charged HAp particles of Chen 2011 would result in the adsorption of adhesive proteins, as these are known electrostatic interactions.
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Claim(s) 16, 19, 21 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Sunami et al. (Published: 2019. WIPO Patent Publication: WO 2019168000 A1. Filed in IDS 6/24/2024, Cite No 1.), in view of Zandi et al. (Published: 2010. J. Biomed. Mater. Res., 92A: 1244-1255) as applied to claims 16 and 21, in further view of Chase et al. (Published: 2012. Stem Cells Transl Med. 2012 Oct;1(10):750-8.).
With regard to claims 16 and 21, the combined teachings of Sunami and Zandi render obvious the claimed methodology of claim 16, and the claimed product of claim 21, as iterated above in the 103 rejection the content of which is incorporated in claims 16 and 21.
However, the combined teachings of Sunami and Zandi do not teach that the medium containing the adhesive protein is serum-free as required by claims 19 and 23.
Chase teaches that culturing mesenchymal stem cells in serum-free medium allows for continual propagation while maintaining potency (Abstract, “Human MSCs expanded in SFM-XF showed continual propagation, with an expected phenotype and differentiation potential… The SFM-XF culture system allows better expansion and multipotentiality of MSCs and serves as a preferred alternative to serum-containing media for the production of large scale, functionally competent MSCs for future clinical applications.”).
It would have been obvious for a skilled artisan to modify the non-woven sheet taught by Zandi and Sunami, to further utilize serum-free medium to improve proliferation of mesenchymal stem cells while maintaining its potent nature. There would have been reasonable expectations of success in combining these teachings as one of ordinary skill in the art would recognize to combine known elements in the art to give predictable results.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Katriel B Kasayan whose telephone number is (571)272-1402. The examiner can normally be reached 10-4p.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria G Leavitt can be reached at (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KATRIEL BARCELLANO KASAYAN/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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