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 .
Applicant’s perfection of foreign priority regarding the reference Matsusaki et al (WO2018143286) has required the finality of the rejection of the last Office action to be withdrawn. Therefore, a Non-final Office action is presented below.
Status of the Claims
Claims 1, 3-10 and 12-22 are currently pending.
Claims 1, 3-4, 9-10, 12, 14, 17, and 19-20 have been amended.
Claims 12-14 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claims 2 and 11 has been cancelled
Claims 21-22 are newly added.
Claims 1, 3-10 and 15-22 have been considered on the merits.
Priority
Receipt is acknowledged of the certified copy of translation of the JP2019-069972, required by 37 CFR 1.55.
Withdrawn Rejections
All of the rejections made under 35 U.S.C. 103 have been withdrawn in light of Applicant’s perfection of foreign priority regarding the reference Matsusaki et al (WO2018143286).
New Rejections
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, 3-5, 9-10, 19, and 22 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Kelly et al (US20170232144A1).
Claim Interpretation: Claim 1 recites the limitations of a fragmented collagen component having an average length of 5 µm to 50 µm and an average diameter of 50 nm to 30 µm. Therefore, a collagen particle which has a spherical shape with a diameter of anywhere between 5 µm to 30 µm would read on the fragmented collagen component of claim 1 having an average length of 5 µm to 50 µm and an average diameter of 50 nm to 30 µm.
Regarding claim 1, Kelly teaches a method of producing a three-dimensional tissue construct ([0003]), comprising culturing cells in an injectable liquid gel base including fragmented collagen components derived from cartilage extracellular matrix (ECM) ([0006]/[0053]/[0116]), fibrin ([0050]), and an aqueous medium ([0102]). Kelly also teaches a step of mixing fibrinogen before culturing with the fragmented collagen components and adding thrombin to cause gelation as required by claim 1 ([0118]). Kelly teaches that the fragmented collagen components have an average particle size of 10-200 microns which meets the limitations of claim 1, wherein the fragmented collagen component has an average length of 5 µm to 50 µm and an average diameter of 50 nm to 30 µm ([0014]). More specifically, Kelly teaches a particle size of between 10-30 µm which falls within the overlap of the claimed length and diameter measurements ([0014]/[0033]). Additionally, Kelly teaches that the collagen components are derived from a non-human animal as required by claim 1 ([0094]).
Regarding claim 3, Kelly teaches that the components are cross-linked ([0011]).
Regarding claim 4, Kelly teaches a fragmented collagen particle size of between 10-30 µm which falls within the claimed length of between 10-50 µm ([0014]/[0033]).
Regarding claim 5, Kelly teaches that the cells are extracellular matrix producing cells ([0053]/[0054]).
Regarding claim 9, Kelly teaches that the content of the fragmented collagen components is 1-200 mg/ml which corresponds to a mass% of 0.1-20 mass% which falls within the range of 0.33-90 mass% ([0116]).
Regarding claim 10, Kelly teaches that the content of the fragmented collagen components is 1-200 mg/ml which corresponds to a mass% of 0.1-20 mass% which falls within the range of 0.5-90 mass% ([0116]).
Regarding claims 19 and 22, Kelly teaches mixing fibrinogen with the fragmented collagen components and mixing thrombin as an activator mixture and then combining the fibrinogen mixture with the thrombin activator mixture to obtain the culture injectable liquid gel base ([0050]-[0052]).
Therefore, Kelly anticipates the claims.
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.
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, 6-7, 15, 18, and 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Kelly et al (US20170232144A1), in view of Bhatia (US20080181935A1; reference of record).
Regarding claims 6-7, 15, 18, and 20, the limitations of the independent claim have been taught above by Kelly.
Regarding claim 20, Kelly teaches first mixing fibrinogen with the fragmented collagen components and second mixing thrombin as an activator mixture and then combining the fibrinogen mixture with the thrombin activator mixture to obtain the culture injectable liquid gel base ([0050]-[0052]).
Regarding claim 21, Kelly teaches that the collagen components are crosslinked by heat ([0103]), and the content of the fragmented collagen components is between 0.1-20% which meets the limitations of the claimed range of 0.22 to 1 mass% ([0116]).
Kelly does not teach that the cells further comprise one or more kinds of cells selected from vascular endothelial cells, cancer cells, cardiomyocytes, smooth muscle cells, fibroblasts and epithelial cells as required by claim 6. Kelly does not teach that the cells comprise at least vascular endothelial cells and fibroblasts as required by claim 7. Kelly does not teach wherein the culture liquid is in the form of liquid droplets as required by claim 15. Kelly does not teach wherein the cells are uniformly distributed in the three dimensional tissue construct as required by claim 18. Kelly does not teach that the cells include vascular endothelial cells as required by claim 21.
However, Bhatia teaches about method of preparing compositions employing collagen for the augmentation or replacement of mammalian tissue (abstract). Bhatia, like Kelly, teaches a form of fragmented collagen component by tissue homogenization ([0089]), however Bhatia does not disclose the particle size or dimensions. However, Bhatia states that the “collagen composition of the invention is expected to have an enhanced clinical utility as a wound dressing, for augmenting or replacing hard and/or soft tissue repair, as compared to other biomaterials known in the art” ([0245]).
Regarding claims 6-7, Bhatia teaches that cells which can be included in the liquid culture are fibroblasts, endothelial cells, and stem cells (extracellular matrix producing cells) as required by claims 6-7 ([0187]/[0148]).
Regarding claim 15, Bhatia teaches that the culture liquid is in the form of liquid droplets ([0182]).
Regarding claim 18, Bhatia teaches that the cells are uniformly distributed in the three-dimensional tissue construct ([0144]).
One of ordinary skill in the art would find it obvious at the time of the effective filling date to combine the method of making 3D collagen-based tissue construct taught by Kelly and the method of making a collagen-based tissue constructs taught by Bhatia to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Bhatia states that the “collagen composition of the invention is expected to have an enhanced clinical utility as a wound dressing, for augmenting or replacing hard and/or soft tissue repair, as compared to other biomaterials known in the art” ([0245]). One of ordinary skill in the art would have a reasonable expectation of success when combining Kelly with Bhatia because both Kelly and Bhatia teach the formation of 3D tissue constructs from collagen constructs and Bhatia teaches the necessary information for the culturing of additional cell types such as fibroblasts, endothelial cells, and stem cells.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, especially in the absence of evidence to the contrary.
Claims 1, 8, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Kelly et al (US20170232144A1), in view of Bhatia (US20080181935A1; reference of record), as applied to claims 1, 6-7, 15, 18, and 20-21 above, and in further view of Li et al (Journal of Cancer, 2011, reference of record).
Regarding claims 8 and 16, the limitations of the independent claim 1 are taught above.
Bhatia teaches that the cells are fibroblasts as required by claim 16 ([0187]/[0148]).
Kelly and Bhatia do not teach that the content of the fibroblasts is greater than or equal to 25% based on a number of whole cells as required by claims 8 and 16.
However, Li teaches a method co-culturing fibroblast cells with epithelial cancer cells on 3D culture systems with different ratios of fibroblasts. Li reports optimizing the ratio of fibroblasts to epithelial cells to form spheroids with the desired characteristics (pg. 462, column 1, para. 1). Li teaches ratios of fibroblasts including 16.6%, 33.3% and 50% fibroblasts as required by claims 8 and 16 (pg. 462, column 1, para. 1).
One of ordinary skill in the art would find it obvious at the time of the effective filling date to modify the method and fibroblasts taught by Kelly and Bhatia with the fibroblast ratios taught by Li to arrive at the instant invention. One of ordinary skill in the art would find it obvious to make this modification because Li teaches that “[t]he higher the ratio of fibroblasts (MEF) in the mixture, the more ductal/tubular network formed among the aggregates” (pg. 462, col. 1, para 1). One of ordinary skill in the art would have a reasonable expectation of success when combining Li with Kelly and Bhatia because Bhatia teaches that cells included in the liquid culture could be fibroblasts and epithelial cells and Li teaches the successful 3D culture of fibroblasts and epithelial cells, forming physiologically relevant networks.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, especially in the absence of evidence to the contrary.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Kelly et al (US20170232144A1), in view of Bhatia (US20080181935A1; reference of record), and Li et al (Journal of Cancer, 2011, reference of record).
Claim Interpretation: Claim 1 recites the limitations of a fragmented collagen component having an average length of 5 µm to 50 µm and an average diameter of 50 nm to 30 µm. Therefore, a collagen particle which has a spherical shape with a diameter of anywhere between 5 µm to 30 µm would read on the fragmented collagen component of claim 1 having an average length of 5 µm to 50 µm and an average diameter of 50 nm to 30 µm.
Regarding claim 17, Kelly teaches a method of producing a three-dimensional tissue construct ([0003]), comprising culturing cells in an injectable liquid gel base including fragmented collagen components derived from cartilage extracellular matrix (ECM) ([0006]/[0053]/[0116]), fibrin ([0050]), and an aqueous medium ([0102]). Kelly also teaches a step of mixing fibrinogen before culturing with the fragmented collagen components and adding thrombin to cause gelation as required by claim 17 ([0118]). Kelly teaches that the fragmented collagen components have an average particle size of 10-200 microns which meets the limitations of claim 17, wherein the fragmented collagen component has an average length of 5 µm to 50 µm and an average diameter of 50 nm to 30 µm ([0014]). More specifically, Kelly teaches a particle size of between 10-30 µm which falls within the overlap of the claimed length and diameter measurements ([0014]/[0033]). Additionally, Kelly teaches that the collagen components are derived from a non-human animal as required by claim 17 ([0094]).
Kelly does not teach wherein the culture liquid is in the form of liquid droplets or that the cells include fibroblasts as required by claim 17.
However, Bhatia teaches about method of preparing compositions employing collagen for the augmentation or replacement of mammalian tissue (abstract). Bhatia, like Kelly, teaches a form of fragmented collagen component by tissue homogenization ([0089]), however Bhatia does not disclose the particle size or dimensions. However, Bhatia states that the “collagen composition of the invention is expected to have an enhanced clinical utility as a wound dressing, for augmenting or replacing hard and/or soft tissue repair, as compared to other biomaterials known in the art” ([0245]).
Regarding claim 17, Bhatia teaches that cells which can be included in the liquid culture are fibroblasts, endothelial cells, and stem cells (extracellular matrix producing cells) ([0187]/[0148]).
Regarding claim 17, Bhatia teaches that the culture liquid is in the form of liquid droplets ([0182]).
One of ordinary skill in the art would find it obvious at the time of the effective filling date to combine the method of making 3D collagen-based tissue construct taught by Kelly and the method of making a collagen-based tissue constructs taught by Bhatia to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Bhatia states that the “collagen composition of the invention is expected to have an enhanced clinical utility as a wound dressing, for augmenting or replacing hard and/or soft tissue repair, as compared to other biomaterials known in the art” ([0245]). One of ordinary skill in the art would have a reasonable expectation of success when combining Kelly with Bhatia because both Kelly and Bhatia teach the formation of 3D tissue constructs from collagen constructs and Bhatia teaches the necessary information for the culturing of additional cell types such as fibroblasts, endothelial cells, and stem cells.
Kelly and Bhatia do not teach wherein the content of the fibroblasts is greater than or equal to 25% based on a number of whole cells as required by claim 17.
However, Li teaches a method co-culturing fibroblast cells with epithelial cancer cells on 3D culture systems with different ratios of fibroblasts. Li reports optimizing the ratio of fibroblasts to epithelial cells to form spheroids with the desired characteristics (pg. 462, column 1, para. 1). Li teaches ratios of fibroblasts including 16.6%, 33.3% and 50% fibroblasts as required by claim 17 (pg. 462, column 1, para. 1).
One of ordinary skill in the art would find it obvious at the time of the effective filling date to modify the method and fibroblasts taught by Kelly and Bhatia with the fibroblast ratios taught by Li to arrive at the instant invention. One of ordinary skill in the art would find it obvious to make this modification because Li teaches that “[t]he higher the ratio of fibroblasts (MEF) in the mixture, the more ductal/tubular network formed among the aggregates” (pg. 462, col. 1, para 1). One of ordinary skill in the art would have a reasonable expectation of success when combining Li with Kelly and Bhatia because Bhatia teaches that cells included in the liquid culture could be fibroblasts and epithelial cells and Li teaches the successful 3D culture of fibroblasts and epithelial cells, forming physiologically relevant networks.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant’s arguments, see Remarks, filed 01/12/2026, with respect to the rejection(s) of claim(s) 1, 3-10, and 15-22 under 35 U.S.C 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Kelly (US20170232144A1).
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CONSTANTINA E STAVROU whose telephone number is (571)272-9899. The examiner can normally be reached M-F 8:00-5:00.
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CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/ANOOP K SINGH/Primary Examiner, Art Unit 1632