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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/09/2026 has been entered.
Claims 14, 17, 19-30 and 32-36 are pending in this application, Claims 29, 30 and 33-36 are acknowledged as withdrawn, Claims 14, 17, 19-28 and 32 were examined on their merits.
The objection to Claim 14 because of minor informalities has been withdrawn due to the Applicant’s amendments to the claims filed 02/09/2026.
The rejection of Claim 14 under 35 U.S.C. § 103 as being unpatentable over Son et al. (US 2017/0274018 A1), as evidenced by Buchtova et al. (2015), both cited in the IDS, and evidenced by Kaur et al. (2015), of record, has been withdrawn due to the Applicant’s amendments to the claims filed 02/09/2026.
Response to Amendment
The Declaration under 37 CFR 1.132 filed 02/09/2026 is insufficient to overcome the rejection of claims 14, 17, 19-28 and 32 based upon Son et al. (US 2017/0274018 A1) as set forth in the last Office action and below because:
The Declarant argues that Son allegedly never teaches loading re-differentiated cells on a chitosan-based 3D scaffold (Declaration, Pg. 2, #5 and Pg. 3, #s 8&9).
This is not found to be persuasive for the following reasons, as discussed in the below rejections, Son teaches a method (of forming artificial cartilage) wherein chondrocytes are cultured/passaged in an FGF containing (dedifferentiation) medium to obtain MSC-like dedifferentiated cells (Pg. 13, Claims 1-2); culturing the MSC-like dedifferentiated cells in a chondrogenic (redifferentiation) medium that does not contain FGF in an adherent chitosan based 3-D scaffold in chondrogenic medium (Pg. 13, Claim 3 and Pg. 3, Paragraph [0044] and Pg. 13, Claim 5 and Pg. 7, Paragraph [0104] and Pg. 12, Paragraph [0215] and Fig. 29).
Buchtova et al. makes obvious the substitution of FGF2 for the FGF of Son et al. and it would have been obvious to those of ordinary skill in the art to modify the method of Son et al. of 3D culturing the MSC-like dedifferentiated cells in a chondrogenic redifferentiation medium to perform the culturing under adherent conditions because cells may only be cultured under adherent or non-adherent conditions. This is the choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; see KSR and the MPEP at 2143, I, E. The Examiner has interpreted the prior art two-step process of culturing MSC-like dedifferentiated cells in a chondrogenic (redifferentiation) medium that does not contain FGF in a chitosan based 3D scaffold in chondrogenic medium as meeting the limitations of Claim 14, ii) and iii) because the combined culturing of dedifferentiated chondrocytes under adherent, 3D conditions in a medium which does not contain FGF.
The Declarant argues that the ordinary artisan would not consider loading on a scaffold the product of a pellet culture (Declaration, Pg. 4, #10).
This is not found to be persuasive as neither the current rejections or citations reference pellet culturing or the loading thereof on a scaffold.
The Declarant argues that Son discloses two alternative two-step methods for obtaining artificial cartilage while the instant invention requires 3 steps including an intermediate step of 2D culture before 3D culture (Declaration, Pg. 4, #s11-12 and Pg. 5, #s 13-14 and Pg. 6, #15).
This is not found to be persuasive for the following reasons, the instant claims only require: culturing adherent chondrocytes in a dedifferentiation medium comprising FGF2, and then culturing in an FGF-free redifferentiation medium in an adherent/3D culture system. The prior art teaches culturing the MSC-like dedifferentiated cells in a chondrogenic (redifferentiation) medium that does not contain FGF in a chitosan based 3-D scaffold, and combined with the other cited prior art, makes obvious the substitution of FGF2 for FGF and culturing the dedifferentiated FGF2 treated chondrocytes under adherent 3D conditions in the absence of FGF2, thus meeting the limitations of Claim 14, steps ii) and iii), particularly in the absence of a showing of new or unexpected results.
The Declarant argues that the disclosure compared the claimed 3-step method to a control 2-step method (alleged to be similar to the method of Son); of a first 2D culture of chondrocytes in a medium containing FGF-2 and a second 3D culture step of chondrocytes in a medium containing no FGF-2. Declarant submits the claimed method produced cartilage with an increased GAG content and higher expression of type II collagen as compared to the control (Declaration, Pgs. 6-7, #s 16-19).
This is not found to be persuasive for the following reasons, the 2-step method of the disclosure does not represent a comparison with the closest prior art, see the MPEP at 716.02(e), III., which is the method of Son of: a first 2D culture of chondrocytes in a medium containing FGF2 and then a second 3D culture step of those chondrocytes in a medium containing no FGF2.
The Examiner notes that neither the description of Fig. 5A in the published Specification at Pg. 3, Paragraph [0025] or the figure itself indicate that the first culture was performed under 2D adherent conditions and the second culture under 3D adherent conditions. The figure and description merely indicate that unspecified culturing was performed first in a medium (E) containing FGF2 (as well as a multitude other components, see the Specification as filed at Pgs. 25-26, Table 1), than culturing in a medium without FGF2 (I) (but comprised of a multitude other components, see the Specification as filed at Pgs. 25-26, Table 1). Further, the allegation of increased GAG content was from an experiment performed under different oxygen concentrations, a feature not found in the instant claims and therefore not commensurate in scope with the claimed invention. See the MPEP at 716.02(d).
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.
Claims 14, 19, 20, 23, 24, 26, 27, 32 and 35 are rejected under 35 U.S.C.
§ 103 as being unpatentable over Son et al. (US 2017/0274018 A1), in view of
Buchtova et al. (2015), both cited in the IDS, and evidenced by Kaur et al. (2015) and
Fisher (2025), both of record.
Son et al. teaches a method (of forming artificial cartilage) wherein chondrocytes are cultured/passaged in adherent 2D culture in an FGF containing (dedifferentiation) medium to obtain MSC-like dedifferentiated cells (Pg. 13, Claims 1-2 and Pg. 12, Paragraph [0209]), and reading on Claim 14, step i);
then culturing the MSC-like dedifferentiated cells in a chondrogenic (redifferentiation) medium that does not contain FGF in a chitosan based 3D scaffold in chondrogenic medium (Pg. 13, Claim 3 and Pg. 3, Paragraph [0044] and Pg. 13, Claim 5 and Pg. 7, Paragraph [0104] and Pg. 12, Paragraphs [0211]&[0215] and Fig. 29), and reading on Claim 14, steps ii) and iii).
It would be inherent in the method of Son et al. that the chondrocytes cultured in dedifferentiation media are cultured under adherent conditions because they are treated with trypsin-EDTA upon reaching confluence (Pg. 6, Paragraph [0083]). Kaur et al. evidences that trypsin-EDTA is used for the enzymatic detachment of adherent cells (Pg. 119, Column 2, Lines 9-13).
Son et al. does not specifically teach that the MSC-like dedifferentiated chondrocytes are cultured in an adherent, 3D culture system, as required by Claim 14, ii) and iii);
The teachings of Son et al. were discussed above.
Son et al. did not teach a method wherein the dedifferentiation medium comprises FGF-2 and the redifferentiation/maturation culture medium is free of FGF-2, as required by Claim 14;
wherein the redifferentiation/maturation culture medium comprises TGF-ß, as
required by Claim 19;
wherein the redifferentiation/maturation culture medium comprises TGF-ß3, as
required by Claim 20;
wherein the dedifferentiation medium comprises serum, as required by Claim 23;
wherein the induction/maturation medium comprises insulin, transferrin and
selenium, as required by Claim 24;
wherein the chondrocytes are cultured in step i) for 10-15 days, in step ii) for 4-8
days and/or in step iii) for 10-15 days, as required by Claim 26;
wherein the chondrocytes are isolated from a subject, as required by Claims 27
and 32;
wherein hyaline cartilage tissue is produced in vitro and administered in a
therapeutically effective amount to the subject, as required by Claim 32;
or wherein the produced hyaline cartilage tissue is a spheroid and presents
glycosaminoglycan (GAG) content of between 10 and 100ug/spheroid, as required by
Claim 35.
Buchtova et al. teaches that FGF activates WNT/B-catenin signaling in
chondrocytes and specifically exemplifies FGF2 (Pg. 841, Paragraph 2.1 and Lines 33-
36).
It would have been obvious to those of ordinary skill in the art to modify the
method of Son et al. of 3D culturing the MSC-like dedifferentiated cells in a chondrogenic redifferentiation medium to perform the culturing under adherent conditions because cells may only be cultured under adherent or non-adherent conditions. This is the choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; see KSR and the MPEP at 2143, I, E. The Examiner notes that the reference teaches seeding chondrocytes on scaffolds (3D culture form) and culturing (Pg. 8, Paragraph [0130]), thus implying the cells are adhered to the scaffold. The ordinary artisan would have been motivated to make this
modification because this would allow cells to grow and produce cartilage in a defined area. There would have been a reasonable expectation of success in making this modification because there are only a finite number of ways to culture cells and the reference implies 3D culturing of chondrocytes under adherent conditions.
It would have been obvious to those of ordinary skill in the art to modify the
method of Son et al. of culturing the MSC-like dedifferentiated cells in a chondrogenic
redifferentiation medium under adherent conditions because cells may only be cultured
under adherent or non-adherent conditions.
This is the choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; see KSR and the MPEP at 2143, I., E. The ordinary artisan would have been motivated to make this modification because while Son et al. may exemplify non-adherent culturing, the method is not limited to that method. There would have been a reasonable expectation of success in making this modification because the method teaches both adherent and non-adherent culture methods.
It would have been further obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Son et al. wherein chondrocytes are cultured/passaged in an FGF containing dedifferentiation medium to obtain MSC-like dedifferentiated cells (Pg. 13, Claims 1-2) to use FGF2 as taught by Buchtova et al. because the method of Son et al. is not limited to any particular FGF and Buchtova et al. teaches that FGF2 is a suitable FGF for use on chondrocytes.
Those of ordinary skill in the art would have been motivated to make this modification in order to treat chondrocytes with a suitable FGF. There would have been a reasonable expectation of success in making this modification because Son et al. treats chondrocytes with FGF generally and Buchtova et al. teaches the treatment of chondrocytes with FGF2 specifically.
With regard to Claim 14, the Examiner has interpreted the prior art two-step process of culturing MSC-like dedifferentiated cells in a chondrogenic (redifferentiation) medium that does not contain FGF in a chitosan based 3D scaffold in chondrogenic medium as meeting the limitations of Claim 14, ii) and iii) because the combined 3D culturing of dedifferentiated chondrocytes is obvious under adherent conditions.
With regard to the limitation of Claim 14, i) of "a dedifferentiation culture medium
that activates Wnt signaling pathway to obtain chondrocytes with a morphology of
fibroblastic-like cells", Son et al. teaches that during in vitro expansion chondrocytes become morphologically fibroblastic shaped (Pg. 5, Paragraph [0070]). Son et al. further teaches the chondrocyte dedifferentiation medium contains FGF. Buchtova et al. evidences that FGF2 activates the canonical Wnt pathway in chondrocytes (Pg. 839,
Abstract). Thus, it would be inherent in the method of Son et al. that the FGF treated, in vitro cultured chondrocytes would have a morphology of fibroblastic-like cells.
With regard to the limitation of Claim 14, iii) of "induction/maturation medium that
maintain the inactivation of Wnt signaling pathway", Son et al. teaches loading the
re-differentiated cells on a chitosan-based 3D scaffold in a medium that does not
contain FGF. Thus, it would be inherent in the method of Son et al. that the 3D cultured
differentiated cells would maintain the inactivation of the Wnt signaling pathway as
claimed. See above, where Buchtova et al. evidences that FGF/FGF2 activates the canonical Wnt pathway in chondrocytes (Pg. 839, Abstract), thus the absence of FGF would be expected to maintain inactivation of the Wnt signaling pathway.
With regard to Claims 19 and 20, Son et al. teaches the redifferentiation/maturation culture medium comprises TGF-β3 (Pg. 7, Paragraph
[0104]).
With regard to Claim 23, Son et al. teaches dedifferentiation medium is Cambrex
MSCGM-FGF (Pg. 6, Paragraph [0081]). Fisher evidences that Lonza (formerly
Cambrex) MSCGM contains FBS (Pg. 1, Specifications).
With regard to Claim 24, Son et al. teaches the induction/maturation medium
comprises insulin, transferrin and selenium (ITS+3) (Pg. 7, Paragraph [0104]).
With regard to Claim 26, while the references listed above do not specifically
teach the limitation wherein the chondrocytes are cultured in step i) during 10-15 days,
in step ii) during 4-8 days and/or in step iii) during 10-15 days, one of ordinary skill in
the art would recognize that the culture time for each step is a result-effective
optimizable variable. Son et al. teaches that dedifferentiated chondrocytes are cultured
in redifferentiation medium for 2-3 weeks. This is a starting point for the determination of a useful culture time range which encompasses the claimed range. This is motivation for someone of ordinary skill in the art to practice or test the culture time values widely to find those that are functional or optimal to sufficiently provide a suitable number of cells which then would be inclusive or cover the instantly claimed values/culture times.
Absent any teaching of criticality by the Applicant concerning the culture time, it would be prima facie obvious that one of ordinary skill in the art would recognize these limitations are an optimizable variable which can be met as a matter of routine optimization (see MPEP § 2144.05 (II)(B). Those of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to make this modification in order to obtain culture of chondrocytes with the desired number of cells. There would have been a reasonable expectation of success in making this modifications because Son et al. is drawn at least to the in vitro culture of differentiated chondrocytes for a certain period of time.
With regard to Claims 27 and 32, Son et al. teaches the isolation of chondrocytes
from rabbit subjects (Pg. 5, Paragraph [0075]).
With regard to Claim 32, Son et al. teaches producing cartilage tissue in vitro
(Pg. 6, Paragraph [0088]) and administering a therapeutically effective amount to a
subject (Pg. 7, Paragraph [0120] and Pg. 8, Paragraph [0145]).
With regard to Claim 35, Son et al. teaches the cartilage tissue produced is
hyaline (Pg. 11, Paragraph [0188]), is in the form of a spheroid (Fig. 16) and presents a
GAG content of about 0.4-0.9 µg/300µl (Fig. 18B).
Claims 14, 17, 19, 20, 23, 24, 26, 27, 32 and 35 are rejected under 35
U.S.C. § 103 as being unpatentable over Son et al. (US 2017/0274018 A1), in view of
Buchtova et al. (2015), both cited in the IDS, and evidenced by Kaur et al. (2015) and
Fisher (2025), both of record, as applied to Claims 14, 19, 20, 23, 24, 26, 27, 32
and 35 above, and further in view of Narcisi et al. (2012), of record.
The teachings of Son et al. and Buchtova et al. were discussed above.
Neither reference taught a method wherein the dedifferentiation medium further
comprises at least one growth factor selected from the group consisting of: PDGF-BB,
EGF and TGF-B, as required by Claim 17.
Narcisi et al. taught a method wherein chondrocytes are treated with a
dedifferentiation medium comprising FGF-2, EGF and PDGF-BB (Pg. 1153, Column 1,
Lines 52-60).
It would have been obvious to those of ordinary skill in the art before the effective
filing date of the claimed invention to modify the method of Son et al. and Buchtova et
al. wherein chondrocytes are cultured/passaged in an FGF-2 containing
dedifferentiation medium to obtain MSC-like dedifferentiated cells to further include EGF
and PDGF-BB in the dedifferentiation medium as taught by Narcisi et al. because the
prior art recognizes these growth factors along with FGF-2 as suitable components for
chondrocyte dedifferentiation media. Those of ordinary skill in the art would have been motivated to make this modification in order to treat chondrocytes with a suitable dedifferentiation medium. There would have been a reasonable expectation of success in making this modification because Son et al. treats chondrocytes with FGF to induce dedifferentiation, Buchtova et al. teaches treating chondrocytes with FGF-2 to induce dedifferentiation, and Narcisi et al. teaches treating chondrocytes with FGF-2, EFG and PDGF-BB to induce dedifferentiation.
Claims 14, 19, 20, 21, 23, 24, 26, 27, 32 and 35 are rejected under 35 U.S.C. § 103 as being unpatentable over Son et al. (US 2017/0274018 A1), in view of Buchtova et al. (2015), both cited in the IDS, and evidenced by Kaur et al. (2015) and Fisher (2025), both of record, as applied to Claims 14, 19, 20, 23, 24, 26, 27, 32 and 35 above, and further in view of Pomohac (WO 2008/086147 A1), of record.
The teachings of Son et al. and Buchtova et al. were discussed above.
Neither reference taught a method wherein the redifferentiation medium further
comprises TGF-B and FGF-7, as required by Claim 21.
Pomohac teaches a "chondroinductive agent" or "chondroinductive factor" refers
to any natural or synthetic, organic or inorganic chemical or biochemical compound or
combination or mixture of compounds, or any mechanical or other physical device,
container, influence or force that can be applied to any cells, progenitor cells or stem
cells so as to effect their in vitro differentiation, for example into chondrocytes or
cartilage or the production of cartilaginous tissue, wherein the chondroinductive agent
may be TGF-83 and Keratinocyte Growth Factor (KGF or FGF-7) (Pgs. 10-11, Paragraph [0044]).
It would have been obvious to those of ordinary skill in the art before the effective
filing date of the claimed invention to modify the method of Son et al. and Buchtova et
al. wherein MSC-like dedifferentiated cells are cultured in a chondrogenic
(redifferentiation) medium to include TGF-8 and FGF-7 as taught by Pomohac because
the reference teaches that TGF-8 and FGF-7 are known chondroinductive/differentiation
agents. Those of ordinary skill in the art would have been motivated to make this
modification because Son et al. teaches a redifferentiation medium to induce
chondrocyte differentiation and Pomohac teaches that TGF-B and FGF-7 are known
agents to induce chondrocyte differentiation.
Claims 14, 19, 20, 22, 23, 24, 26, 27, 32 and 35 are rejected under 35 U.S.C. § 103 as being unpatentable over Son et al. (US 2017/0274018 A1), in view of Buchtova et al. (2015), both cited in the IDS, and evidenced by Kaur et al. (2015) and Fisher (2025), both of record, as applied to Claims 14, 19, 20, 23, 24, 26, 27, 32 and 35 above, and further in view of Kaps et al. (2002), of record.
The teachings of Son et al. and Buchtova et al. were discussed above.
Neither reference taught a method wherein the redifferentiation medium
comprises platelet lysate, as required by Claim 22.
Kaps et al. teaches that treatment of chondrocytes treated with platelet lysate
(PL) showed stimulated growth and that PL is suitable for chondrocyte expansion (Pg.
485m Abstract).
It would have been obvious to those of ordinary skill in the art before the effective
filing date of the claimed invention to modify the method of Son et al. and Buchtova et
al. wherein MSC-like dedifferentiated cells are cultured in a chondrogenic
(redifferentiation) medium to include platelet lysate in the medium as taught by Kaps et
al. because the reference teaches that PL is known to stimulate chondrocyte growth in
vitro.
Those of ordinary skill in the art would have been motivated to make this
modification because Son et al. teaches a redifferentiation medium to induce
chondrocyte differentiation and Kaps et al. teaches that PL will stimulate the growth of
those chondrocytes in culture.
Claims 14, 19, 20, 23, 24, 25, 26, 27, 32 and 35 are rejected under 35 U.S.C. § 103 as being unpatentable over Son et al. (US 2017/0274018 A1), in view of Buchtova et al. (2015), both cited in the IDS, and evidenced by Kaur et al. (2015) and Fisher (2025), both of record, as applied to Claims 14, 19, 20, 23, 24, 26, 27, 32 and 35 above, and further in view of Shi et al. (2013), of record.
The teachings of Son et al. and Buchtova et al. were discussed above.
Neither reference taught a method wherein the 3D cultured chondrocytes are
cultured in hypoxia atmosphere comprising less than 10% O2 (v/v), as required by Claim 25.
Shi et al. teaches that 3D chondrocyte spheroids cultured under hypoxic
conditions (5% O2) exhibit positive effects on the sustaining of chondrocytes phenotype
and expressions of collagen Il and aggrecan at protein and gene levels, indicating the
essential roles of biomimetic microenvironment in vitro in maintaining the tissue specific
functions in cartilage.
Both hypoxic condition and 3D construction were prerequisite for in vitro cartilage
engineering and tissue repair. It is also clinically necessary to select the superior
chondrocytes by providing the physiologically relevant microenvironment before
chondrocyte implantations (Pg. 5, Column 1, Lines 10-22).
It would have been obvious to those of ordinary skill in the art before the effective
filing date of the claimed invention to modify the method of Son et al. and Buchtova et
al. wherein redifferentiated chondrocyte cells are cultured on a chitosan based 3-D
scaffold to further culture the cells under hypoxia as taught by Shi et al. because the
reference teaches 3D culture and hypoxia are necessary for sustaining chondrocytes
phenotype in vitro and mimicking in vivo conditions. Those of ordinary skill in the art
would have been motivated to make this modification because Son et al. teaches the
3D culture of redifferentiated chondrocytes and Shi et al. teaches that hypoxic and 3D
culture conditions are necessary for chondrocytes to maintain their phenotype in vitro,
which is necessary for in vivo applications. There would have been a reasonable
expectation of success in making this modification because at least both Son et al. and
Shi et al. are both drawn to the same field of endeavor, the culture of chondrocytes.
Claims 14, 19, 20, 23, 24, 26, 27, 28, 32 and 35 are rejected under 35 U.S.C. § 103 as being unpatentable over Son et al. (US 2017/0274018 A1), in view of Buchtova et al. (2015), both cited in the IDS, and evidenced by Kaur et al. (2015) and Fisher (2025), both of record, as applied to Claims 14, 19, 20, 23, 24, 26, 27, 32 and 35 above, and further in view of Stockwell et al. (1967), of record.
The teachings of Son et al. and Buchtova et al. were discussed above.
Neither reference taught a method wherein the chondrocytes are isolated from
human cartilage tissue, as required by Claim 28.
Stockwell teaches that human beings have chondrocyte containing costal
cartilage (Pg. 753, Abstract),
It would have been obvious to those of ordinary skill in the art before the
effective filing date of the claimed invention to modify the method of Son et al. and
Buchtova et al. wherein chondrocytes are obtained from rabbit costal cartilage to use
human costal cartilage as taught by Stockwell because both sources are recognized
chondrocyte containing cartilage. Those of ordinary skill in the art would have been
motivated to make this modification because both rabbit and human costal cartilage are
recognized sources of chondrocytes. There would have been a reasonable expectation
of success in making this modification because both rabbit and human cartilage
contains the cells of interest.
Response to Arguments
Applicant’s arguments, see Remarks, filed 02/09/2026, with respect to the above withdrawn objection/rejection have been fully considered and are persuasive.
Applicant's remaining arguments filed 02/09/2026 have been considered only insofar as they apply to the new rejections herein.
The Applicant argues, citing the Declaration, that Son teaches a two-step method of forming cartilage (Remarks, Pg. 10, Lines 1-21 and Pg. 11, Lines 1-15).
This is not found to be persuasive for the following reasons, as discussed in the above rejections, Son teaches a method (of forming artificial cartilage) wherein chondrocytes are cultured/passaged in an FGF containing (dedifferentiation) medium to obtain MSC-like dedifferentiated cells (Pg. 13, Claims 1-2); culturing the MSC-like dedifferentiated cells in a chondrogenic (redifferentiation) medium that does not contain FGF in an adherent chitosan based 3-D scaffold in chondrogenic medium (Pg. 13, Claim 3 and Pg. 3, Paragraph [0044] and Pg. 13, Claim 5 and Pg. 7, Paragraph [0104] and Pg. 12, Paragraph [0215] and Fig. 29). Buchtova et al. makes obvious the substitution of FGF2 for the FGF of Son et al. and it would have been obvious to those of ordinary skill in the art to modify the method of Son et al. of 3D culturing the MSC-like dedifferentiated cells in a chondrogenic redifferentiation medium to perform the culturing under adherent conditions because cells may only be cultured under adherent or non-adherent conditions. This is the choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; see KSR and the MPEP at 2143, I, E.
The Examiner has interpreted the prior art two-step process of culturing MSC-like dedifferentiated cells in a chondrogenic (redifferentiation) medium that does not contain FGF in a chitosan based 3D scaffold in chondrogenic medium as meeting the limitations of Claim 14, ii) and iii) because it obviates the combined culturing of dedifferentiated chondrocytes under adherent, 3D conditions in a medium which does not contain FGF2.
The Applicant argues, citing the Declaration, that the claimed “3-step” process
produced hyaline cartilage with an increased GAG content and higher expression of type II collagen as compared to the control (Remarks, Pg. 11, Lines 16-21 and Pg. 12, Lines 16-20).
This is not found to be persuasive for the following reasons, the 2-step control method of the disclosure does not represent a comparison with the closest prior art, see the MPEP at 716.02(e), III., which is the method of Son of: a first 2D culture of chondrocytes in a medium containing FGF2 and then a second 3D culture step of those chondrocytes in a medium containing no FGF2. The Examiner notes that neither the description of Fig. 5A in the published Specification at Pg. 3, Paragraph [0025] or the figure itself indicate that the first culture was performed under 2D adherent conditions and the second culture under 3D adherent conditions. The figure and description merely indicate that unspecified culturing was performed first in a medium (E) containing FGF2 (as well as a multitude other components, see the Specification as filed at Pgs. 25-26, Table 1), than culturing in a medium without FGF2 (I) (but comprised of a multitude other components, see the Specification as filed at Pgs. 25-26, Table 1).
Further, the allegation of increased GAG content was from an experiment performed under different oxygen concentrations, a feature not found in the instant claims and therefore not commensurate in scope with the claimed invention. See the MPEP at 716.02(d).
The Applicant argues that there is nothing in Son to teach or suggest to the ordinary artisan to modify the two-step method to add a third step, and that neither Buchtova or Kaur remedy the alleged deficiencies of Son (Remarks, Pg. 12, Lines 1-24 and Pg. 16, Lines 17-23).
This is not found to be persuasive for the following reasons, as discussed above, the Examiner is not suggesting modifying the method of Son from a two-step to three-step method but rather that the two-step method makes obvious the limitations of the claimed method. Buchtova was cited only for its’ teaching that FGF activates WNT/B-catenin signaling in chondrocytes and specifically exemplifies FGF2 while Kaur was cited only as evidence that trypsin-EDTA is used for the enzymatic detachment of adherent cells.
The Applicant argues that Fisher does not remedy the alleged deficiencies of Son, Buchtova and Kaur (Remarks, Pg. 13, Lines 1-7).
This is not found to be persuasive for the reasoning provided in the above rejections. The Examiner notes that Fisher was cited only as evidence that Lonza (formerly Cambrex) MSCGM contains FBS (Pg. 1, Specifications).
The Applicant argues that Narcisi does not remedy the alleged deficiencies of Son, Buchtova Kaur and Fisher (Remarks, Pg. 13, Lines 11-28).
This is not found to be persuasive for the reasoning provided in the above rejections. The Examiner notes that Narcisi was cited only for its’ teaching of a method wherein chondrocytes are treated with a dedifferentiation medium comprising FGF2, EGF and PDGF-BB.
The Applicant argues that Pomohac does not remedy the alleged deficiencies of Son, Buchtova Kaur and Fisher (Remarks, Pg. 14, Lines 1-20).
This is not found to be persuasive for the reasoning provided in the above rejections.
The Examiner notes that Pomohac was cited only for its’ teaching that a "chondroinductive agent" or "chondroinductive factor" refers to any natural or synthetic, organic or inorganic chemical or biochemical compound or combination or mixture of compounds, or any mechanical or other physical device, container, influence or force that can be applied to any cells, progenitor cells or stem cells so as to effect their in vitro differentiation, for example into chondrocytes or cartilage or the production of cartilaginous tissue, wherein the chondroinductive agent may be TGF-83 and Keratinocyte Growth Factor (KGF or FGF-7).
The Applicant argues that Kaps does not remedy the alleged deficiencies of Son, Buchtova Kaur and Fisher (Remarks, Pg. 14, Lines 21-29 and Pg. 15, Lines 1-9).
This is not found to be persuasive for the reasoning provided in the above rejections. The Examiner notes that Kaps was cited only for its’ teaching that treatment of chondrocytes treated with platelet lysate (PL) showed stimulated growth and that PL is suitable for chondrocyte expansion (Pg. 485m Abstract).
The Applicant argues that Shi does not remedy the alleged deficiencies of Son, Buchtova Kaur and Fisher (Remarks, Pg. 15, Lines 10-28).
This is not found to be persuasive for the reasoning provided in the above rejections.
The Examiner notes that Shi was cited only for its’ teaching that 3D chondrocyte spheroids cultured under hypoxic conditions (5% O2) exhibit positive effects on the sustaining of chondrocytes phenotype and expressions of collagen Il and aggrecan at protein and gene levels, indicating the essential roles of biomimetic microenvironment in vitro in maintaining the tissue specific functions in cartilage. Both hypoxic condition and 3D construction were prerequisite for in vitro cartilage engineering and tissue repair. It is also clinically necessary to select the superior chondrocytes by providing the physiologically relevant microenvironment before chondrocyte implantations.
The Applicant argues that Stockwell does not remedy the alleged deficiencies of Son, Buchtova Kaur and Fisher (Remarks, Pg. 15, Lines 10-28).
This is not found to be persuasive for the reasoning provided in the above rejections. The Examiner notes that Stockwell was cited only for its’ teaching that that human beings have chondrocyte containing costal cartilage.
No claims are allowed.
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/PAUL C MARTIN/Examiner, Art Unit 1653 04/01/2026
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