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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 03/26/2025 has been entered.
Claim Status
1. The Amendment filed 03/26/2025 has been entered. Claims 1 – 3 and 5 – 31 remain pending. Claim 4 has been cancelled.
Election/Restrictions
2. Applicant’s election without traverse of Group I (claims 1 – 10) in the reply filed on 05/29/2024 is acknowledged.
3. Claims 11 – 31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/29/2024.
Priority
4. This application is the 35 U.S.C. 371 national stage filing of International Application No.
PCT/SI2018/050035, filed 12/20/2018.
Claims Under Consideration
5. Claims 1 – 3 and 5 – 10 are under consideration.
Withdrawn Claim Rejections
6. The rejection of claim 4 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 is rendered moot by Applicant’s cancellation of the claim.
7. The rejection of claims 1 – 3 and 5 – 10 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in view of Applicant’s amendment to the claims.
8. The rejection of claim 4 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 is rendered moot by Applicant’s cancellation of the claim.
9. The rejection of claim 4 under 35 U.S.C. 103 as being unpatentable over Kobayashi (US-9057052-B2; previously cited), hereinafter Kobayashi in view of Sehaqui (Sehaqui, H, et al. ACS Sustainable Chemistry & Engineering 4.9 (2016): 4582-4590), hereinafter Sehaqui in view of Mertaniemi (Mertaniemi, H, et al. Biomaterials 82 (2016): 208-220), hereinafter Mertaniemi is rendered moot by Applicant’s cancellation of the claim.
10. The rejection of claims 1 – 3, 7, and 8 under 35 U.S.C. 103 as being unpatentable over Kobayashi (US-9057052-B2; previously cited), hereinafter Kobayashi in view of Sehaqui (Sehaqui, H, et al. ACS Sustainable Chemistry & Engineering 4.9 (2016): 4582-4590), hereinafter Sehaqui in view of Mertaniemi (Mertaniemi, H, et al. Biomaterials 82 (2016): 208-220), hereinafter Mertaniemi is withdrawn in view of Applicant’s amendment to the claims.
11. The rejection of claims 5, 6, and 9 under 35 U.S.C. 103 as being unpatentable over Kobayashi (US-9057052-B2; previously cited), hereinafter Kobayashi in view of Sehaqui (Sehaqui, H, et al. ACS Sustainable Chemistry & Engineering 4.9 (2016): 4582-4590), hereinafter Sehaqui in view of Mertaniemi (Mertaniemi, H, et al. Biomaterials 82 (2016): 208-220), hereinafter Mertaniemi as applied to claims 1 – 4, 7, and 8 above, and further in view of Guo (Guo, J, et al. Biomacromolecules 18.3 (2017): 898-905.), hereinafter Guo in view of Orelma (Orelma, H, et al. Biointerphases 7.1 (2012)), hereinafter Orelma is withdrawn in view of Applicant’s amendment to the claims.
12. The rejection of claim 10 under 35 U.S.C. 103 as being unpatentable over Kobayashi (US-9057052-B2; previously cited), hereinafter Kobayashi in view of Sehaqui (Sehaqui, H, et al. ACS Sustainable Chemistry & Engineering 4.9 (2016): 4582-4590), hereinafter Sehaqui in view of Mertaniemi (Mertaniemi, H, et al. Biomaterials 82 (2016): 208-220), hereinafter Mertaniemi as applied to claims 1 – 4, 7, and 8 above, and further in view of Legeay (US-20130131828-A1; previously cited), hereinafter Legeay in view of Hoque (Hoque, ME, et al. Tissue Engineering Part A 15.10 (2009): 3013-3024.), hereinafter Hoque in view of Strobbe (US-20130196375-A1; previously cited), hereinafter Strobbe in view of Calandrelli (Calandrelli, L., et. al. J Mater Sci: Mater Med 21, 2923–2936 (2010)), hereinafter Calandrelli in view of Lui (Lui, C. N. P., et al. Angewandte Chemie International Edition 52.47 (2013): 12298-12302; previously cited), hereinafter Lui in view of Stergar (Stergar, J., et al J Sol-Gel Sci Technol (2017) 88:57–65; previously cited), hereinafter Stergar in view of Ferk (Ferk, G, et al. Journal of alloys and compounds 648 (2015): 53-58.), hereinafter Ferk is withdrawn in view of Applicant’s amendment to the claims.
New Rejections
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.
13. Claims 1 – 3 and 5 – 10 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.
14. Claim 1 recites “the membrane consists of a 3D printed carrier structure comprising”. The metes and bounds of “consists” (close-ended) and “comprising” (open-ended) are unclear because it raises confusion as to the composition of the membrane regarding whether additional elements are excluded. Claims 2 – 3 and 5 – 10 are also rejected as the depend from claim 1 and do not clarify the grounds of rejection.
15. Claim 10 depends from claim 1 and recites “the membrane includes”. The metes and bounds of “includes” is unclear because it raises confusion as to the composition of the membrane as claim 1 recites “the membrane consists of”. “Includes” is open-ended and does not exclude additional elements (see MPEP 2111.03).
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.
16. Claim(s) 1 – 3 and 7 – 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lee (Lee, HyeongJin, et al. Tissue Engineering Part C: Methods 19.10 (2013): 784-793.), hereinafter Lee in view of Coleman (US20130252336-A1; Filed 05/16/2013; Published 09/26/2013), hereinafter Coleman which is cited on the IDS filed 06/07/2024 in view of Oliveira (Oliveira, Catarina, et al. Biomacromolecules 15.6 (2014): 2196-2205.), hereinafter Oliveira in view of Xie (Xie, Hui, et al. PeerJ 4 (2016): e2040.), hereinafter Xie.
Regarding claims 1 – 3 and 7, Lee teaches 3D printed multi-layered structure of alginate (“3D printed carrier structure”, “at least one layer of biocompatible polymer” of claim 1” and “alginate” of claim 7) and polycaprolactone (S-1, S-2, and S-3 in Figure 1) where the pore size of each of the S-1, S-2, and S-3 structures is greater than 300 µm but less than 500 µm (“diameter in the range from 200 to 500 µm” of claim 1) (Abstract; Figure 1; page 785, right col. paragraph 1 and 5; page 786, left col. paragraph 3; Figure 3; page 787, right col. paragraph 3 – 4). Figure 3b (shown below) shows the S-1 structure comprises multiple layers of polycaprolactone (PCL) struts arranged in a structured geometry (“woven and nonwoven materials” of claim 1, “a structured geometry with a shape, size and distribution of the pores uniform throughout the layer” of claim 2 and “several layers of structured” of claim 3). Applicant’s specification (page 7 – 8) discloses alginate and polycaprolactone are suitable biocompatible polymers (“inert” of claim 1).
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Lee does not teach “integrated target molecules are covalently bound to the surface and/or in the pores of said carrier structure” of claim 1 or claim 8. However, Lee teaches tissue engineering is a rapidly growing interdisciplinary research area that may provide options for treating damaged tissues and organs (page 784, left col. paragraph 1). Lee teaches to be able to obtain ultimate functionality, a biomedical scaffold should achieve homogenous cell distribution in its interior structure and the S-1, S-2, and S-3 structures are able to support cell growth after 30 days (page 791, right col., Figure 5).
Regarding “integrated target molecules are covalently bound to the surface and/or in the pores of said carrier structure” of claim 1 and claim 8, Coleman teaches a three-dimensional matrix for capture of target cells where the matrix includes a capture ligand that can be an antibody or an antigen binding fragment that has a binding affinity for a cell surface molecule (page 1, 0005, 0007; Figure 1A). Coleman teaches the matrix can capture stem cells (page 2, 0020). Coleman teaches in Figure 1A (shown below) the matrix comprises a structured geometry with pore size of 200 – 400 µm where antibodies are located in the pores and where target cells bind to the antibodies.
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Coleman teaches the capture ligand may be indirectly attached to the three-dimensional matrix (page 3, 0022) but does not teach “covalently bound” of claim 1. However, Coleman teaches the matrix can be composed of alginate and polycaprolactone (page 1, 0006; page 3, 0028). Coleman teaches rapid isolation of target cells from fluid cell-containing samples that include blood, lipoaspirate, and bone marrow aspirate (page 2, 0019). Coleman teaches the matrix can have a porosity that retains cells of a certain size while allowing others to pass through the matrix (page 3, 0021).
Regarding “covalently bound” target molecules of claim 1, Oliveira teaches covalently bound antibodies to activated polycaprolactone comprising surface amine groups to enable the binding of molecules from a biological fluid (Abstract; page 2197, left col. paragraph 5 – 6 and right col. paragraph 1 – 4; page 2198, right col. last paragraph; page 2204, left col. last paragraph). Oliveira teaches immobilizing multiple antibodies targeting different antigens (page 2197, right col. paragraph 3 – 4). Oliveira teaches covalently bound antibodies to polycaprolactone may be used in tissue engineering and regenerative medicine fields due to surface binding of the antibody target (page 2204, right col. paragraph 1).
Xie teaches a 3D printed construct of alginate and polycaprolactone (PCL) with bone marrow-derived mesenchymal stem cells (BMSCs) (Figure 1; page 3, last paragraph; page 4, paragraph 1). Xie teaches isolation of BMSCs from bone marrow where BMSCs are positive for CD105, CD73, CD29 and CD44 and are negative for CD34 and CD45 (Figure 2; page 4, paragraph 2). Xie teaches BMSC-alginate-PCL constructs implanted in mice increase bone formation compared to alginate-PCL without BMSCs (Figure 5). Xie teaches it is necessary to improve the proangiogenic ability of bone tissue engineering scaffolds (page 2, paragraph 1).
It would have been obvious prior to the effective filing date for the person of ordinary skill in the art to combine the teachings of Lee regarding alginate-polycaprolactone layered structures with the teachings of Coleman regarding a matrix that includes an antibody for capture of target cells with the teachings of Oliveira regarding covalently bound antibodies to polycaprolactone with the teachings of Xie regarding an alginate-PCL-BMSC construct for regrowing bone in vivo to arrive at the claimed composition consisting of a 3D printed structure comprising at least one layer of alginate-polycaprolactone with pores that have a diameter of 300 – 500 µm with covalently bound antibodies capable of binding to antigens on the surface of BMSCs. One would have been motivated to combine the teachings of Lee, Coleman, Oliveira, and Xie in a construct to capture BMSCs for tissue engineering as Lee teaches tissue engineering is a rapidly growing interdisciplinary research area that may provide options for treating damaged tissues and organs, Oliveira teaches covalently bound antibodies to polycaprolactone may be used in tissue engineering and regenerative medicine fields, and Xie teaches it is necessary to improve the proangiogenic ability of bone tissue engineering scaffolds. One would have a reasonable expectation of success in combining the teachings as Coleman teaches the matrix that can be comprised of alginate and polycaprolactone can capture stem cells and Xie teaches BMSC-alginate-PCL constructs implanted in mice increase bone formation.
17. Claim(s) 5, 6, and 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lee (Lee, HyeongJin, et al. Tissue Engineering Part C: Methods 19.10 (2013): 784-793.), hereinafter Lee in view of Coleman (US20130252336-A1; Filed 05/16/2013; Published 09/26/2013), hereinafter Coleman which is cited on the IDS filed 06/07/2024 in view of Oliveira (Oliveira, Catarina, et al. Biomacromolecules 15.6 (2014): 2196-2205.), hereinafter Oliveira in view of Xie (Xie, Hui, et al. PeerJ 4 (2016): e2040.), hereinafter Xie as applied to claims 1 – 3 and 7 – 8 above, and further in view of Kim (Kim, Jung-Ju, et al. Rsc Advances 4.33 (2014): 17325-17336.), hereinafter Kim in view of Odabas (Odabaş, S., et al. Journal of Chromatography B 861.1 (2008): 74-80.), hereinafter Odabas.
Lee in view of Coleman, Oliveira, and Xie make obvious the limitations of claim 1 as set forth above. Lee, Coleman, Oliveira, and Xie do not teach claims 5 and 9. However, Xie teaches BMSCs from bone marrow where BMSCs are positive for CD105, CD73, CD29 and CD44 and are negative for CD34 and CD45 (Figure 2; page 4, paragraph 2).
Regarding claim 6, Lee teaches a 3D structure made of several layers of alginate and polycaprolactone with structured geometry with pores of 300 – 500 µm (Abstract; Figure 1; page 785, right col. paragraph 1 and 5; page 786, left col. paragraph 3; Figure 3; page 787, right col. paragraph 3 – 4). Lee does not teach “integrated functionalized nanoparticles to which target molecules are covalently bound via the surface functional groups”.
Regarding “functionalized nanoparticles integrated” of claim 5, “integrated functionalized nanoparticles” of claim 6, and claim 9, Kim teaches composite porous scaffolds of polycaprolactone (PCL) and carboxyl group surface functionalized magnetite nanoparticles (“inorganic”, “magnetic”, “metal”, “metal oxide”, “functionalized nanoparticles have on their surface at least one functional group” of claim 9) (magnetic scaffolds) where the nanoparticles were well-distributed within the PCL matrix to enable homogenous nanocomposites with pores ranging from 250 – 500 µm (Abstract; page 17326, left col. paragraph 1 – 3; page 17327, right col. paragraph 3; page 17328, left col. paragraph 1 – 2 and right col. paragraph 1; Figure 2; page 17330, left col. paragraph 1; page 17335, left col. paragraph 2 and right col.; Table 2). Kim does not teach “whereby target molecules are covalently bound onto the functionalized nanoparticles via their surface functional groups” of claim 5 or “to which target molecules are covalently bound via their surface functional groups: of claim 6. However, Kim teaches the magnetic scaffolds showed favorable tissue compatibility in vivo and thus support their use for bone repair and regeneration (Abstract). Kim teaches engineering scaffolds with properties to improve cell adhesion, growth and development into specific tissues is the key issue in scaffold development for tissue engineering (page 17325, right col. paragraph 1).
Regarding “whereby target molecules are covalently bound onto the functionalized nanoparticles via their surface functional groups” of claim 5 or “to which target molecules are covalently bound via their surface functional groups: of claim 6, Odabas teaches magnetite nanoparticles functionalized with surface carboxyl groups to which CD105 and CD73 antibodies are covalently bound for separation of mesenchymal stem cells (MSCs) from cell suspensions including bone marrow (Abstract; Figure 1C – D; page 75, right col. 4 – 6; page 76, left col. last paragraph; page 77, left col. paragraph 2 – 4; page 78, left col. paragraph 2 – 3). Odabas teaches the immobilization of CD79 and CD105 antibodies to the nanoparticles was achieved with well-known carbodiimide chemistry with coupling efficiencies of 79.85% and 77.98%, respectively (page 77, right col. paragraph 4). Odabas teaches separation of CD105+ stem cells with the functionalized nanoparticles was greater than commercially available CD105 microbeads and quite high separation efficiencies were achieved (Table 2; page 78, right col. paragraph 2 – 3; page 80, left col. paragraph 2). Odabas teaches the first step in stem cell therapies is to obtain the required amount of specific stem cells where they have to be isolated and cultured in vitro in order to increase their number (page 74, right col. paragraph 2). Odabas teaches MSCs can be isolated from bone marrow where they represent a very small fraction of the total nucleated cell (page 74, right col. paragraph 2). Odabas proposes separating the target cells by magnetic nanoparticles and then culture them directly (page 80, left col. paragraph 1).
It would have been obvious prior to the effective filing date for the person of ordinary skill in the art to combine the teachings of Lee regarding alginate-polycaprolactone layered structures with the teachings of Coleman regarding a matrix that includes an antibody for capture of target cells with the teachings of Oliveira regarding covalently bound antibodies to polycaprolactone with the teachings of Xie regarding an alginate-PCL-BMSC construct for regrowing bone in vivo with the teachings of Kim regarding composite porous scaffolds of PCL and carboxyl group surface functionalized magnetite nanoparticles with the teachings of Odabas regarding covalently bound antibodies to magnetite nanoparticles to arrive at the claimed composition where magnetite nanoparticles functionalized with carboxyl groups to which antibodies to BMSC surface antigens are covalently bound are integrated into the PCL structure. One would have been motivated to combine the teachings of Lee, Coleman, Oliveira, Xie, Kim, and Odabas in a construct to capture BMSCs for tissue engineering as Kim teaches engineering scaffolds with improved properties is the key issue in scaffold development for tissue engineering and Odabas teaches the first step in stem cell therapies is to obtain the required amount of specific stem cells where they have to be isolated. One would have a reasonable expectation of success in combining the teachings as Kim teaches the magnetic scaffolds showed favorable tissue compatibility in vivo and thus support their use for bone repair and regeneration and Odabas teaches quite high separation efficiencies of CD105+ and CD73+ stem cells from bone marrow.
18. Claim(s) 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lee (Lee, HyeongJin, et al. Tissue Engineering Part C: Methods 19.10 (2013): 784-793.), hereinafter Lee in view of Coleman (US20130252336-A1; Filed 05/16/2013; Published 09/26/2013), hereinafter Coleman which is cited on the IDS filed 06/07/2024 in view of Oliveira (Oliveira, Catarina, et al. Biomacromolecules 15.6 (2014): 2196-2205.), hereinafter Oliveira in view of Xie (Xie, Hui, et al. PeerJ 4 (2016): e2040.), hereinafter Xie as applied to claims 1 – 3 and 7 – 8 above, and further in view of Calandrelli (Calandrelli, L., et. al. J Mater Sci: Mater Med 21, 2923–2936 (2010); previously cited), hereinafter Calandrelli in view of Qhobosheane (Qhobosheane, Monde, et al. Analyst 126.8 (2001): 1274-1278), hereinafter Qhobosheane in view of Stergar (Stergar, J., et al J Sol-Gel Sci Technol (2017) 88:57–65; previously cited), hereinafter Stergar in view of Odabas (Odabaş, S., et al. Journal of Chromatography B 861.1 (2008): 74-80.), hereinafter Odabas.
Lee in view of Coleman, Oliveira, and Xie make obvious the limitations of claim 1 as set forth above. Lee teaches a 3D printed layer-by-layer structure consisting of eight layers of polycaprolactone (PCL) with structured geometry with fixed pore size of 500 µm (“structured geometry and made of polycaprolactone”) (page 785, right col. paragraph 5; page 787, right col. paragraph 3; Figure 3a). Lee does not teach “ten layers” or “with integrated functionalized nanoparticles of NiCu enclosed by a layer of silica with NH2 functional groups on the surface onto which the target molecules are bound”.
Regarding “ten layers”, Coleman teaches in Figure 1A the matrix for stem cell capture comprises a structured geometry with pore size of 200 – 400 µm where antibodies are located in the pores and where target cells bind to the antibodies. It would have been obvious to combine the teachings of Lee regarding eight layers of PCL with structured geometry with the teachings of Lee regarding a matrix for stem cell capture using antibodies to cell surface antigens to arrive at the claimed ten layers. One would have been motivated to combine the teachings for a ten layered structure because adding two additional layers to the structure of Lee would provide more cell capture sites to increase the number of target cells captured. One would have a reasonable expectation of success in combining the teachings for a ten layered structure as Lee teaches the structure is formed by layer-by-layer 3D printing and Coleman teaches rapid isolation of target cells from fluid cell-containing samples that include blood, lipoaspirate, and bone marrow aspirate. Coleman does not teach “with integrated functionalized nanoparticles of NiCu enclosed by a layer of silica with NH2 functional groups on the surface onto which the target molecules are bound”.
Regarding “integrated functionalized nanoparticles”, Calandrelli teaches nanocomposites of PCL and functionalized silica nanoparticles (Abstract; page 2923, right col. last paragraph; page 2924, left col. last paragraph and right col. last paragraph). Calandrelli teaches the silica particles have been functionalized with vinyl end group but not a NH2 group (page 2924, right col. last paragraph). However, Calandrelli teaches silica is generally inert in the body and can be modified easily using a variety of well-established chemical reactions including reaction with DETA to introduce NH2 groups on the surfaces of silica nanoparticles (page 2323, right col. paragraph 2 – 3). Calandrelli teaches bone marrow comprises mesenchymal stem cells (MSCs) that can give rise to precursors for bone (page 2924, left col. paragraph 2). Calandrelli teaches an ideal bone tissue engineering strategy implies the use of autologous bone marrow MSCs (page 2924, left col. paragraph 3). Calandrelli teaches PCL/silica nanocomposites appear promising for bone tissue engineering (page 2395, left col. last paragraph). Calandrelli does not teach “NiCu enclosed by a layer of silica”.
Regarding “NH2 functional groups on the surface onto which the target molecules are bound”, Qhobosheane teaches silica nanoparticles with NH2 functional groups on the surface onto which enzymes are bound (Scheme 1; page 1275, right col. paragraph 1 – 3; page 1276, right col. paragraph 2). Qhobosheane teaches silica nanoparticles are a good biocompatible support for enzyme immobilization as they show excellent enzymatic activity (Abstract). Qhobosheane does not teach “NiCu enclosed by a layer of silica”.
Regarding “NiCu enclosed by a layer of silica ” nanoparticles, Stergar teaches NiCu magnetic nanoparticles in a silica matrix (Abstract; page 58, left col. last paragraph; Figure 1). Stergar teaches NiCu nanoparticles are sustainable nanomaterials which are chemically stable, biocompatible and exhibit desired magnetic properties making them highly interesting for use in biomedicine (page 58, left col. paragraph 3).
Odabas teaches covalently bound CD105 and CD73 antibodies to surface functionalized magnetic nanoparticles for separation of MSCs from cell suspensions including bone marrow (Abstract; Figure 1C – D; page 75, right col. 4 – 6; page 76, left col. last paragraph; page 77, left col. paragraph 2 – 4; page 78, left col. paragraph 2 – 3). Odabas teaches the immobilization of CD79 and CD105 antibodies to the nanoparticles was achieved with well-known carbodiimide chemistry (page 77, right col. paragraph 4). Odabas teaches in Figure 1C coupling between carboxyl and amine groups using EDC (Figure 1C). Odabas teaches separation efficiencies of CD105+ and CD73+ stem cells were achieved (Table 2; page 78, right col. paragraph 2 – 3; page 80, left col. paragraph 2). Odabas teaches the first step in stem cell therapies is to obtain the required amount of specific stem cells where they have to be isolated and cultured in vitro in order to increase their number (page 74, right col. paragraph 2). Odabas teaches MSCs can be isolated from bone marrow where they represent a very small fraction of the total nucleated cell (page 74, right col. paragraph 2). Odabas proposes separating the target cells by magnetic nanoparticles and then culture them directly (page 80, left col. paragraph 1).
It would have been obvious prior to the effective filing date for the person of ordinary skill in the art to combine the teachings of Lee regarding alginate-polycaprolactone layered structures with the teachings of Coleman regarding a matrix that includes an antibody for capture of target cells with the teachings of Oliveira regarding covalently bound antibodies to polycaprolactone with the teachings of Xie regarding an alginate-PCL-BMSC construct for regrowing bone in vivo with the teachings of Calandrelli regarding nanocomposites of PCL and functionalized silica nanoparticles with the teachings of with the teachings of Qhobosheane regarding silica nanoparticles with NH2 functional groups on the surface onto which biomolecules are bound with the teachings of Stregar regarding NiCu magnetic nanoparticles in a silica matrix with the teachings of Odabas regarding covalently bound antibodies to magnetic nanoparticles for MSCs separation to arrive at the claimed composition where ten layers of PCL are integrated with functionalized NiCu nanoparticles enclosed by a layer of silica with NH2 functional groups on the surface onto which antibodies to BMSC surface antigens are covalently bound. One would have been motivated to combine the teachings of Lee, Coleman, Oliveira, Xie, Calandrelli, Qhobosheane, Stergar, and Odabas in a construct to capture BMSCs for tissue engineering as Calandrelli teaches PCL/silica nanocomposites appear promising for bone tissue engineering and Calandrelli teaches an ideal bone tissue engineering strategy implies the use of autologous bone marrow MSCs. One would have a reasonable expectation of success in combining the teachings as Calandrelli teaches silica is generally inert in the body and can be modified easily using a variety of well-established chemical reactions, Qhobosheane teaches silica nanoparticles are a good biocompatible support for biomolecule immobilization, Stergar teaches NiCu nanoparticles are biocompatible and exhibit desired magnetic properties, and Odabas teaches quite high separation efficiencies of CD105+ and CD73+ stem cells from bone marrow with magnetic nanoparticles.
Applicant’s Arguments/ Response to Arguments
19. Applicant Argues: On page 10, Applicant asserts Kobayashi does not teach all of the limitations as currently claimed. On page 10, paragraph 4, Applicant asserts that the prior art teachings of immobilized antibodies would prevent the free flow through the filter and the current disclosure allows for free flow of the suspension through the membrane without the membrane becoming contaminated or clogged due to buildup.
Response to Arguments: This is not found persuasive because the previous rejections using Kobayashi as the primary reference have been withdrawn. In the new rejections set forth above, Lee teaches a structure with pores in the claimed range (Abstract; Figure 1; page 785, right col. paragraph 1 and 5; page 786, left col. paragraph 3; Figure 3; page 787, right col. paragraph 3 – 4) and Coleman teaches a matrix that can have a porosity that retains cells of a certain size while allowing others to pass through the matrix (page 3, 0021). Coleman teaches a matrix with immobilized antibodies that bind cell surface antigens for stem cell capture (Figure 1A).
Conclusion
No claims allowed.
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/Z.M.B./Examiner, Art Unit 1632
/ANOOP K SINGH/Primary Examiner, Art Unit 1632