DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The instant application is a national stage entry under 35 USC 371 of PCT/JP2021/045015, filed
07 December 2021. Acknowledgement is made of Applicant’s claim for foreign priority under 35 USC 119(b) to Japanese application JP2021-006928, filed 20 January 2021. Receipt is acknowledged of certified copies of papers, in a non-English language, required by 37 CFR 1.55.
Status of Claims
Claims 1-9, of record 22 May 2023, are pending.
Information Disclosure Statement
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.
Drawings
The drawings are objected to because the resolution of Figures 1, 3-5, and 7-10 does not allow for examination, as each of the figures lack clarity.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The substitute Specification filed 22 May 2023 is acknowledged and entered into the application file.
Claim Objections
Claims 4-9 are objected to because of the following informalities:
Regarding claims 4-8: Each of claims 4-8 are objected to for being grammatically incorrect. More specifically, the claims are objected to for simply reciting “mature chondrocyte” instead of “a mature chondrocyte” or “mature chondrocytes”.
Appropriate correction is required.
Regarding claim 9: The instant claim is objected to for being grammatically incorrect. More specifically, the claim is objected to for simply reciting “mature chondrocyte” instead of “a mature chondrocyte” or “mature chondrocytes”.
In addition, the Examiner recommends amending Lines 4-6 to instead recite “...the method includes a step of producing the composition containing the mature chondrocyte as set forth in the method according to claim 4”, or the like.
Appropriate correction is required.
Claim Interpretation
The Examiner would like to note that the transitional term “contain” or “containing” is synonymous with “comprise” or “comprising”. Therefore, the claim language is inclusive or open-ended and may include additional, unrecited elements or method steps. See MPEP § 2111.03(I).
In addition, instant claims 7-8 each recite an intended use limitation. Intended use limitations are considered only in so far as they physically limit the claimed composition. Therefore, even if a composition of the prior art is not explicitly disclosed as being utilized for the recited applications, so long as the prior art composition is physically capable of being used for those applications it will thereby read on the claimed composition produced by the method of claim 4.
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 2-9 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 2: The instant claim recites the limitation "the harvesting cartilage" in Line 2. There is insufficient antecedent basis for this limitation in the claim, as there is no prior recitation of a “harvesting cartilage” within the instant claim or parent claim 1, and parent claim 1 requires multiple “cartilages”. Accordingly, a claim is indefinite when it contains words or phrases whose meaning is unclear. See In re Packard, 751 F.3d 1307, 1314, 110 USPQ2d 1785, 1789 (Fed. Cir. 2014). The lack of clarity could arise if two different levers are recited earlier in the claim, the recitation of "said lever" in the same or subsequent claim would be unclear where it is uncertain which of the two levers was intended. MPEP § 2173.05(e).
Appropriate correction is required.
Regarding claim 3: The instant claim recites the limitation "the cells" in Line 2. There is insufficient antecedent basis for this limitation in the claim, as there is no prior recitation of a “cells” within the instant claim or parent claim 1. See MPEP § 2173.05(e).
Appropriate correction is required.
Regarding claims 4-9: Instant claim 4 recites the limitation “… a composition containing mature chondrocyte obtaining step to get the mature chondrocyte and factors from it…”. The scope of the claim is indefinite, as this recited limitation is wholly unclear, which may be result of the translation from the original language. Therefore, the ordinary artisan cannot readily determine the metes and bounds of the claim.
Instant claims 5-9 either directly depend from or otherwise incorporate the limitations of instant claim 4, thereby rendering them indefinite as well.
Appropriate correction is required.
For purposes of compact prosecution, the Examiner is interpreting this limitation as requiring the mature chondrocytes to be comprised within in a culture medium, wherein the factors inherently secreted from the mature chondrocytes are released into the culture medium.
Regarding claim 6: The instant claim recites the limitation "the conditioned medium" in Line 3. There is insufficient antecedent basis for this limitation in the claim, as there is no prior recitation of a “conditioned medium” within the instant claim or parent claim 4. See MPEP § 2173.05(e).
In addition, the instant claim is rejected to for the use of parentheticals “growth related gene (GRO)” in Line 3. While parentheticals can be used as abbreviations, the use of parentheticals adjacent to terms which recite alternate names or isoforms renders the claim indefinite because it is not clear whether the items within the parentheticals are required or optional.
Appropriate correction is required.
Regarding claim 8: The phrase "or the like" renders the claim indefinite because the claim includes elements not actually disclosed (those encompassed by "or the like"), thereby rendering the scope of the claim unascertainable. See MPEP § 2173.05(d).
Appropriate correction is required.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 4, and 7-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yanaga et al (US 2017/0306294 A1, of record on IDS filed 22 May 2023).
It is of note that although Yanaga et al share the same joint inventors and Assignee as the instant application, Yanaga et al was published more than one year prior to the effective filing date of the instant invention. Therefore, Yanaga et al is considered prior art under 35 USC 102(a)(1).
Yanaga et al disclose methods for the serum-free culture of human cartilage cells, or mature chondrocytes, wherein the mature chondrocytes are cultured in a serum-free culture medium comprising FGF-2 and hydrocortisone (Abstract; Paragraphs [0054], [0057], [0065], [0077], [0087], [0095]).
Yanaga et al further disclose that that mature chondrocytes are isolated from auricular cartilage (Paragraphs [0036], [0038]-[0039], [0046], [0085], [0104]-[0106]).
Yanaga et al further disclose that the mature chondrocytes are utilized as transplants in the repair of cartilage within subjects (Paragraphs [0028], [0036], [0060], [0083]-[0107]).
Accordingly, Yanaga et al anticipate the claims as follows:
Regarding claims 1 and 4: Yanaga et al disclose methods for the serum-free culture of mature
chondrocytes, wherein the mature chondrocytes are cultured in a serum-free culture medium comprising FGF-2 and hydrocortisone. As the mature chondrocytes are allowed to sit in the culture medium and will inherently release factors (Paragraphs [0029]-[0035], [0059]), this therefore reads on the methods of instant claims 1 and 4. See MPEP § 2112.
Regarding claim 2: Following the discussion of claim 1, Yanaga et al further disclose that that mature chondrocytes are isolated from auricular cartilage. This therefore reads on the method of the instant claim.
Regarding claims 7-8: Following the discussion of claim 4, Yanaga et al further disclose that the mature chondrocytes are utilized as transplants in the repair of cartilage within subjects. As the mature chondrocytes are physically capable, or suitable, for use in the complete regeneration of cartilage with perichondrium (claim 7) for a mandibular construction (claim 8), for example, this therefore anticipates the methods of the instant claims for the same reasons as discussed in the rejection of instant claim 4. See Claim Interpretation section for the discussion of the intended use limitation.
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.
Claims 1-5 and 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over Yanaga et al (US 2017/0306294 A1, of record on IDS filed 22 May 2023) in view of Lafont et al (Journal of Biological Chemistry, 2007).
The discussion of Yanaga et al regarding claims 1 and 4 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Yanaga et al anticipate claims 1-2, 4, and 7-8. Lafont et al is considered prior art under 35 USC 102(a)(1).
Regarding claims 3 and 5: Following the discussion of claims 1 and 4 above, Yanaga et al further
disclose that the chondrocytes are cultured in 5% CO2 and under hypoxic conditions (Paragraph [0058]).
Yanaga et al further disclose that the chondrocytes are isolated from articular cartilage (Paragraphs [0046], [0064]).
Yanaga et al do not disclose that the hypoxic conditions include 1% or more and 10% or less of oxygen gas against air, as required by instant claims 3 and 5.
Lafont et al, however, disclose the culturing of chondrocytes in a hypoxic environment of 1% O2, wherein the hypoxic conditions allow for the chondrocytes to have an articular phenotype (Pages 4779, 4784).
Therefore, it would have been prima facie obvious to have modified the methods of Yanaga et al such that the mature chondrocytes are cultured in a hypoxic environment of 5% CO2 and 1% O2, as detailed in Lafont et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to culture the chondrocytes in an environment having 1% O2, as it allows for the chondrocytes to have an articular phenotype, and would have had a reasonable expectation of success given that the methods of Yanaga et al suggest culturing the chondrocytes in a hypoxic environment. See MPEP § 2143(I)(G).
Consequently, Yanaga et al as modified by Lafont et al render obvious methods of culturing mature chondrocytes, wherein the mature chondrocytes are cultured in a hypoxic environment of 5% CO2 and 1% O2. This therefore renders obvious the methods of instant claims 3 and 5.
Claims 1-2, 4, and 6-8 are rejected under 35 U.S.C. 103 as being unpatentable over Yanaga et al (US 2017/0306294 A1, of record on IDS filed 22 May 2023) in view of Shastri et al (US 2020/0103409 A1).
The discussion of Yanaga et al regarding claim 4 can be observed above and is relied upon
herein, the content of which is incorporated in its entirety. Yanaga et al anticipate claims 1-2, 4, and 7-8.
Shastri et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2).
Regarding claim 6: As aforementioned in the discussion of claim 4 above, Yanaga et al disclose methods for the serum-free culture of mature chondrocytes, wherein the mature chondrocytes are cultured in a serum-free culture medium comprising FGF-2 and hydrocortisone, and allowed to inherently secrete factors within culture.
Yanaga et al do not disclose that the culture medium comprises IL-8, a growth related gene, MCP-1, and VEGF, as required by instant claim 6.
Shastri et al, however, disclose that chondrocytes secrete each of IL-8, GRO, MCP-1, and VEGF (Paragraphs [0009], [0017], [0097]; Table 1; Figure 1).
Therefore, it would have been prima facie obvious to have substituted the mature chondrocytes of Yanaga et al with the chondrocytes of Shastri et al that inherently secrete each of IL-8, GRO, MCP-1, and VEGF, as doing so would have been a simple substitution of one mature chondrocyte for another. See MPEP § 2143(I)(B). One of ordinary skill in the art before the effective filing date of the invention would have recognized that the two chondrocytes are functionally comparable, as both are derived from articular cartilage (Yanaga et al: Paragraphs [0046], [0064]; Shastri et al: Paragraph [0089]), and thereby would have been able to substitute the mature chondrocytes with predictable results.
Consequently, Yanaga et al as modified by Shastri et al render obvious a method of culturing mature chondrocytes, wherein the mature chondrocytes are allowed to sit in culture and secrete each of IL-8, GRO, MCP-1, and VEGF, such that IL-8, GRO, MCP-1, and VEGF are comprised within the culture medium. This therefore reads on the method of the instant claim.
Claims 1-2, 4, and 7-9 are rejected under 35 U.S.C. 103 as being unpatentable over Yanaga et al (US 2017/0306294 A1, of record on IDS filed 22 May 2023) in view of Hu et al (Dev Dyn, 2016).
The discussion of Yanaga et al regarding claim 4 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Yanaga et al anticipate claims 1-2, 4, and 7-8. Hu et al is considered prior art under 35 USC 102(a)(1).
Regarding claim 9: As aforementioned in the discussion of claim 4 above, Yanaga et al disclose methods for the serum-free culture of mature chondrocytes, wherein the mature chondrocytes are cultured in a serum-free culture medium comprising FGF-2 and hydrocortisone, and allowed to inherently secrete factors within culture.
Yanaga et al further disclose that the chondrocytes are cultured in 5% CO2 and under hypoxic conditions (Paragraph [0058]).
Yanaga et al further disclose that the chondrocytes can be used to repair bone fractures (Paragraph [0060]).
Yanaga et al do not disclose that the mature chondrocytes are comprised within a revascularization promoter composition further comprising VEGFR2-positive cells and cells comprising a vascular inducer, as required by instant claim 9.
Hu et al, however, disclose that chondrocytes express VEGF in a hypoxia-induced manner (Pages 228-229). Hu et al further disclose that VEGF expression within chondrocytes allows for the promotion of revascularization of defected bone (Pages 230-231).
With that, Hu et al disclose that VEGFR2 is the major receptor for transducing VEGF signaling, and that VEGFR2 mediates angiogenesis and promotion of vessel permeability in response to VEGF (Pages 228; 231-232).
Therefore, it would have been prima facie obvious to have modified the method of Yanaga et al such that the mature chondrocytes are cultured in a hypoxic condition to allow for the expression of VEGF, and are further comprised in a composition with cells that express VEGFR2 to allow for the revascularization of bone fractures, as detailed in Hu et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to generate a composition comprising mature chondrocytes that express VEGF and cells that express VEGFR2, as VEGF and VEGFR2 are critical factors for the survival of chondrocytes and their ability to repair bone defects (Hu et al: Pages 228, 230), and would have had a reasonable expectation of success given then combined disclosures of Yanaga et al and Hu et al. See MPEP § 2143(I)(G).
Consequently, Yanaga et al as modified by Hu et al render obvious a method of using mature chondrocytes to promote the revascularization of bone defects, wherein the mature chondrocytes are cultured under hypoxic conditions to allow for the expression of VEGF, and further cultured with cells expressing VEGFR2 to allow for the revascularization of the bone defects. This therefore renders obvious the method of the instant claim, as VEGF is a known vascular inducer. See Paragraph [0014] of instant Specification filed 22 May 2023.
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 1-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of U.S. Patent No. 11,427,808 B2 in view of Lafont et al (Journal of Biological Chemistry, 2007), Shastri et al (US 2020/0103409 A1), Yanaga et al (US 2017/0306294 A1, of record on IDS filed 22 May 2023), and Hu et al (American Association for Anatomy, 2016).
Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims render obvious the instant claims. More specifically, the patent claims are not identical because no single patent claim discloses all of the limitations of any of the instant claims; however, each of the limitations of the instant claims are disclosed by separate patent claims, or rendered obvious by the accompanying prior art. The fact that each of the elements were claimed in the patent application, just not in a single claim, still renders obvious the instant invention because each of the features, though separately claimed, can be physically combined into a single embodiment. It is of note that, although the patent application is directed to a serum-free culture medium for culturing human chondrocytes, instant claim 1 is an obvious variant of the patent claims:
Patent claim 1 is directed to a serum-free culture medium for culturing human chondrocytes, comprising: human auricular cartilage, ITS (a reagent containing insulin, transferrin and sodium selenite), FGF2 (fibroblast growth factor 2) and hydrocortisone, and further comprising SAG (a smoothened agonist) at a concentration of at least 0.01 μM.
Patent claim 4 further limits patent claim 1, requiring the culture medium to further comprise chondrocytes, which are cultured.
Therefore, the combination of patent claims 1 and 4 is an obvious variant of instant claims 1 and 4. More specifically, the ordinary artisan would recognize that the serum-free culture medium for culturing human chondrocytes comprising auricular cartilage (instant claim 2), FGF-2, hydrocortisone, and cultured chondrocytes can be utilized within and encompasses the method steps of instant claims 1 and 4.
Each of the following limitations can be further incorporated into the methods rendered obvious by patent claims 1 and 4:
Lafont et al teach the limitations recited in instant claims 3 and 5.
Shastri et al teach the limitations recited in instant claim 6.
Yanaga et al teach the limitations recited in instant claims 7-8.
Hu et al teach the limitations recited in instant claim 9.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
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/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633