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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 07 November 2025 has been entered.
DETAILED OFFICE ACTION
This Office Action is in response to the papers filed on 07 November 2025
CLAIMS UNDER EXAMINATION
Claims 1, 5-9 and 12-23 are pending and have been examined on their merits.
PRIORITY
EP14000599.2 filed on 20 February 2014, is acknowledged.
WITHDRAWN REJECTIONS
The previous rejections have been withdrawn due to claim amendment.
NEW REJECTIONS
The arguments made in the response filed on 07 November 2025 are acknowledged. New grounds of rejection have been necessitated by claim amendment.
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 6, 14-17 and 20 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.
Claims 6, 14 and 20 recites “mature tissues”. Neither the claims or specification define “mature”. The term “mature” is a relative term which renders the claim indefinite. The term “mature” 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. Appropriate correction is required.
Claim 15 recites “…before expansion or culture”. There is a lack of antecedent basis for “expansion” in base claim 12. The metes and bounds of claim 15 are unclear. Appropriate correction is required. All dependent claims are included in this rejection.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 7-9 and 21-23 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 7 recites “the culturing steps”. The base claim recites culturing in a culture medium, and adding FGF-18 intermittently. It does not explicitly recite multiple culturing steps. Therefore claim 7 is not further limiting. Dependent claims 8-9 are included in this rejection.
Claim 21 recites “the culturing steps”. The base claim recites culturing in a culture medium, and adding FGF-18 intermittently. It does not explicitly recite multiple culturing steps. Therefore claim 21 is not further limiting. Dependent claims 22-23 are included in this rejection.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 5, 7-9, 12-13, 15-19 and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Ellsworth et al. (previously cited; Methods of Administering FGF18. WO2004/032849, 22 April 2004) in view of Tarrant et al. (Methods For Preparation Of Neo-Cartilage Constructs. US20140193468 with benefit of 11/413,419 filed on 28 April 2006) and Gimona et al. (previously cited; Treatment of Cartilage Disorders. WO 2008/023063 28 February 2008).
Ellsworth et al. examine the effect of FGF-18 on chondrocytes in vitro
and in vivo (Objective, page 308). In Figure 3, the art teaches chondrocytes from the human talus joint were isolated from cartilage slices and cultured in the absence of FGF-18 for one week as described under Methods. FGF-18 was added at one week. Figure 3 discloses the cells are subsequently cultured for 4 weeks following FGF18 addition.
The Method section of Ellsworth teaches isolating and culturing chondrocytes from
human talus joints (page 309, left column, last paragraph). The cells are plated in
DMEM in 24-well tissue culture plates (same section). After 24 hours, the cell layers are
rinsed and cultured in serum-free DMEM without additional supplements. A week later,
fresh serum-free DMEM was added with or without FGF18 protein (page 309,
right column, first paragraph). The appropriate media were replaced twice per week and
cell numbers were determined weekly (same cited section). Because Ellsworth teaches
removing media containing FGF18, and replacing it with fresh media
containing FGF-18, the art is interpreted to teach intermittent addition of FGF-
18. Ellsworth teaches micromass culture (hence, 3D culture).
Claim 1 is directed to a process for producing a “transplantable cartilage material”. The
PG Pub of the specification defines a “transplantable cartilage material” as chondrogenic cells, such as chondrocytes prepared for transplantation ([0024]). Ellsworth teaches FGF-18 has a “significant anabolic effect both in vitro and in vivo” (page 317, right column, first full paragraph). Said effect includes increased proliferation and matrix deposition (same section). The art teaches “the anabolic effects of FGF-18 on articular and articular chondrocytes that we have described here suggest that FGF-18 could potentially be useful in promoting repair of damaged cartilages” (page 319, right column, last paragraph). Therefore the chondrocytes prepared by the art interpreted to be a transplantable cartilage material.
Ellsworth teaches intermittent addition of FGF-18, but does not explicitly teach addition for one day per week for at least four weeks.
The art is silent regarding the sequence of the FGF-18 used.
Ellsworth teaches three-dimensional culture, but does not teach a 3D culture suspension.
Tarrant et al. disclose a construct for repairing cartilage (Abstract). Tarrant teaches chondrocytes ([0039]). Tarrant teaches adding a bioactive to a culture medium that promotes production of neo-cartilage and increases activation and proliferation of chondrocytes ([0014] [0105]). The art identifies FGF-18 as a growth factor that increases proliferation of extracellular matrix components, and decreases the amount of donor cartilage required to generate neo-cartilage and reduces culture time ([0015]).
A cell suspension is introduced into a scaffold and subject to a three-dimensional culture ex vivo ([0018] [0165]).
Tarrant also teaches the following:
The use of fibroblast growth factors in systems of the invention produces neo-cartilage in a scaffold without the need for a mechanical stimulus during three-dimensional culturing of chondrocyte ([0015]). Tarrant teaches the use of a culture camber containing culture medium and a supply unit for both continuous and intermittent delivery of culture medium ([0204]).
Gimona et al. teach a method of treating a cartilage disorder and osteoarthritis in particular (Abstract). FGF-18 is a proliferative agent for chondrocytes (see page 8, third paragraph). Chondrocytes are harvested from a joint and cultured with FGF-18 to increase the number of cells prior to transplantation (see page 9, second paragraph). The art teaches the use of human wild-type FGF-18 (page 6, first full paragraph). The Instant Specification discloses human FGF18 is SEQ ID NO: 1.
Gimona teaches the FGF-18 compound is administered in regular intervals once per week (see page 4, fourth paragraph). The art teaches at least 4 consecutive weeks per treatment cycle (page 4, last paragraph).
It would have been obvious to combine the teachings of Ellsworth and Tarrant by culturing chondrocytes in a 3D culture suspension. One would have been motivated to do so since Tarrant teaches the disclosed system produces neo-cartilage in a scaffold without the need for a mechanical stimulus during three-dimensional culturing of chondrocyte. One would have had a reasonable expectation of success since Tarrant teaches chondrocytes may successfully be cultured in 3-dimension. One would have expected similar results since Ellsworth and Tarrant are both directed to treating cartilage defects using chondrocytes treated with FGF-18.
It would have been obvious to combine the teachings of Ellsworth and Gimona by
adding FGF-18 for one day per week and repeating for at least 4 weeks. One
would have been motivated to do so since Ellsworth teaches a method of proliferating a
cartilage material by treating with FGF-18 and Gimona teaches treatment with FGF-18
once weekly for 4 weeks can induce a proliferative response in a cartilage material.
While Gimona teaches administration of FGF-18 to a subject, one would be motivated
to follow the disclosed regimen in vitro since Gimona teaches it has a proliferative effect
in a cartilage material and Ellsworth is directed to proliferation of a cartilage material.
It would have been obvious to use FGF-18 with the claimed sequence since
Gimona teaches FGF-18 with the claimed sequence increases proliferation. One would have had a reasonable expectation of success since Ellsworth and Gimona are both directed to methods of making a cartilage material. Therefore claim 1 is rendered obvious.
Ellsworth teaches chondrocytes (supra). Therefore claim 5 is included in this rejection.
Ellsworth uses cells from a human (supra). Therefore they are interpreted to be harvested from a mammal before culturing. Therefore claim 7 is included in this rejection.
Claim 8 recites the chondrogenic cells are harvested from a mammal to be treated, or from a different mammal. This is an intended use that does not distinguish the cells taught by Ellsworth from the claimed cells. Therefore claim 8 is rejected. Ellsworth teaches human cells. Therefore claim 9 is included in this rejection.
Regarding independent claim 12:
The teachings of Ellsworth as set forth above are reiterated.
Ellsworth teaches intermittent addition of FGF-18, but does not explicitly teach addition for one day per week for at least four weeks.
The art is silent regarding the sequence of the FGF-18 used.
Ellsworth teaches three-dimensional culture, but does not teach a 3D culture suspension.
The art does not teach administering the cells to a mammal as recited in claim 12.
The teachings of Tarrant and Gimona and are reiterated.
It would have been obvious to combine the teachings of Ellsworth and Tarrant by culturing chondrocytes in a 3D culture suspension. One would have been motivated to do so since Tarrant teaches the disclosed system produces neo-cartilage in a scaffold without the need for a mechanical stimulus during three-dimensional culturing of chondrocyte. One would have had a reasonable expectation of success since Tarrant teaches chondrocytes may successfully be cultured in 3-dimension. One would have expected similar results since Ellsworth and Tarrant are both directed to treating cartilage defects using chondrocytes treated with FGF-18.
It would have been obvious to combine the teachings of Ellsworth and Gimona by
adding FGF-18 for one day per week and repeating for at least 4 weeks. One
would have been motivated to do so since Ellsworth teaches a method of proliferating a
cartilage material by treating with FGF-18 and Gimona teaches treatment with FGF-18
once weekly for 4 weeks can induce a proliferative response in a cartilage material.
While Gimona teaches administration of FGF-18 to a subject, one would be motivated
to follow the disclosed regimen in vitro since Gimona teaches it has a proliferative effect
in a cartilage material and Ellsworth is directed to proliferation of a cartilage material. It would have been obvious to use FGF-18 with the claimed sequence since
Gimona teaches FGF-18 with the claimed sequence increases proliferation The skilled artisan would have been motivated to transplant chondrocytes treated with FGF-18 to treat a cartilage disorder, as taught by Gimona. One would have had a reasonable expectation of success since Ellsworth and Gimona are both directed to methods of making a cartilage material. Therefore claim 12 is rendered obvious.
Gimona teaches treating osteoarthritis (Abstract). Therefore claim 13 is included in this
rejection.
Ellsworth obtains cells from a human (mammal) tissue (supra). Therefore claim 15 is
included in this rejection.
The human (mammal) taught by Ellsworth reads on claims 16-17.
Regarding independent claim 18: The preamble of the claim is directed to a method of producing a transplantable cartilage material for autologous chondrocyte implantation. It is noted the preamble is the only difference between claims 1 and 18.
The teachings of the prior art are reiterated. Gimona also teaches autogenous or allogenic cartilage (page 9, first paragraph).
It would have been obvious to prepare cartilage for autologous implantation. Gimona teaches chondrocytes can be obtained from an autologous source. The skilled artisan would do so to treat the same individual the cells are obtained from. One would have had a reasonable expectation of success since Gimona teaches an autologous tissue can be prepared. One would have expected similar results since Ellsworth and Gimona are both directed to methods of making cartilage.
It would have been obvious to combine the teachings of Ellsworth and Tarrant by culturing chondrocytes in a 3D culture suspension. One would have been motivated to do so since Tarrant teaches the disclosed system produces neo-cartilage in a scaffold without the need for a mechanical stimulus during three-dimensional culturing of chondrocyte. One would have had a reasonable expectation of success since Tarrant teaches chondrocytes may successfully be cultured in 3-dimension. One would have expected similar results since Ellsworth and Tarrant are both directed to treating cartilage defects using chondrocytes treated with FGF-18.
It would have been obvious to combine the teachings of Ellsworth and Gimona by
adding FGF-18 for one day per week and repeating for at least 4 weeks. One
would have been motivated to do so since Ellsworth teaches a method of proliferating a
cartilage material by treating with FGF-18 and Gimona teaches treatment with FGF-18
once weekly for 4 weeks can induce a proliferative response in a cartilage material.
While Gimona teaches administration of FGF-18 to a subject, one would be motivated
to follow the disclosed regimen in vitro since Gimona teaches it has a proliferative effect
in a cartilage material and Ellsworth is directed to proliferation of a cartilage material.
It would have been obvious to use FGF-18 with the claimed sequence since
Gimona teaches FGF-18 with the claimed sequence increases proliferation. One would have had a reasonable expectation of success since Ellsworth and Gimona are both directed to methods of making a cartilage material. Therefore claim 18 is rendered obvious.
Ellsworth teaches chondrocytes (supra). Therefore claim 19 is included in this rejection.
Ellsworth harvests cells before culturing (supra). Therefore claim 21 is included in this rejection.
Claim 22 recites the chondrogenic cells are harvested from a mammal to be treated, for from a different mammal. This is an intended use that does not distinguish the cells taught by Ellsworth from the claimed cells. Therefore claim 22 is rejected. Ellsworth teaches human cells. Therefore claim 23 is included in this rejection.
Therefore Applicant’s Invention is rendered obvious as claimed.
Claims 6, 14 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Ellsworth in view if Gimona and Tarrant as cited in the rejection of claims 1 and 12 above, and further in view of Kuo et al. (previously cited; Cartilage tissue engineering: its potential and uses. Current Opinion in Rheumatology 2006, 18:64–73).
Claims 1, 12 and 18 are rejected on the grounds set forth above. The teachings of the prior art are reiterated. Ellsworth teaches chondrogenic cells. The art does note teach mesenchymal stem cells derived from mature tissues.
Kuo teaches cell-based therapy is a promising approach to cartilage regeneration. Different advantages can be derived from potential cell types: primary and chondrocytic cell lines, adult mesenchymal stem cells, and embryonic stem cells (page 64, right column, second paragraph). Kuo teaches one opportunity for overcoming the limited supply of primary chondrocytes is the use of adult mesenchymal stem cells (MSCs) (page 65 “Adult mesenchymal stem cells” section). These cells are easily obtained from bone marrow and possess a multi-lineage potential; that is, they may be induced to differentiate into bone, cartilage, and adipose-like cell types, even after many doublings in culture (same cited section).
It would have been obvious to try using mesenchymal stem cells in the method taught by Ellsworth. One would have been motivated to do so since Ellsworth teaches a method of making a cartilage material and Kuo teaches adult mesenchymal stem cells can be used to produce cartilage (a cartilage material). One would have had a reasonable expectation of success since Kuo teaches adult mesenchymal stem cells can be used to produce cartilage. One would have expected similar results since both references are directed to cartilage materials. Therefore claims 6, 14 and 20 are rendered obvious.
Therefore Applicant’s Invention is rendered obvious as claimed.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE MOSS whose telephone number is (571) 270-7439. The examiner can normally be reached on Monday-Friday, 8am-5pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached on (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is (571) 270-8439.
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/NATALIE M MOSS/ Examiner, Art Unit 1653