DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application is a national stage entry under 35 USC 371 of PCT/EP2022/075828 (filed on 09/16/2022), which claims priority to EUROPEAN PATENT OFFICE (EPO) 21382840.3 (filed on 09/17/2021).
Election/Restrictions
Applicants’ election without traverse of invention group I, drawn to a support suitable for culturing cells in reply filed on 08/05/2026 is acknowledged. Claims 1-15 read on the elected group.
Claims Status
Claims 1-15 and 31-41 are pending.
Claims 31-41 are withdrawn per the election selection filed on 08/05/2026. Claims 1-15 have been examined on the merits.
Claim Interpretation
For clarity of the record the following comments are made regarding claim interpretation under broadest reasonable interpretation:
Regarding claims 2,5,7, and 11, the claims recite product-by-process limitations. Each product-by-process limitations is considered only insofar as the method of production imparts distinct structural or chemical characteristics or properties to the product. Therefore, if the product, as claimed, is the same or obvious over a product of the prior art (i.e. is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process (See, MPEP 2113).
In the instant case, claim 2 is directed to a support according to claim 1. The support of claim 1 is required to be suitable for cell culture, characterized by patterned regions with microbeads attached to the support and the microbeads are modified with at least one functionalizing molecule. Claim 2 states that the patterned regions are defined by a pattern of microbeads is created by allowing the microbeads to adhere to the support when the support is in contact with a stamp, said stamp having protrusions which define the pattern regions within the support, thereby preventing the microbeads from attaching to those areas of the support which are in contact with the stamp protrusions. The result is a support suitable for cell culturing, with patterned regions with microbeads attached to the support, with the microbeads being modified with at least one functionalizing molecule. The method by which the support is created still results in the support described above and in claim 1. Therefore, any support suitable for cell culture, characterized by patterned regions with microbeads attached to the support and the microbeads are modified with at least one functionalizing molecule, would read on this limitation.
For claim 5, the claim is directed to the support of claim 2. Claim 5 states the patterned regions are created using vacuum-driven soft lithography. The resulting support is also the support suitable for cell culture, characterized by patterned regions with microbeads attached to the support and the microbeads are modified with at least one functionalizing molecule, of claims 1 and 2. Therefore, any support suitable for cell culture, characterized by patterned regions with microbeads attached to the support and the microbeads are modified with at least one functionalizing molecule, would read on this limitation.
For claim 7, the claim is directed to the support according to claim 1. The support of claim 1 requires the support suitable for cell culture, characterized by patterned regions with microbeads attached to the support and the microbeads are modified with at least one functionalizing molecule such that, one molecule member is bound to the microbeads and the other is bound to the molecule of interest. Claim 7 states that the microbeads in the support are functionalized by coupling molecular pairing. The result is a support suitable for cell culture, characterized by patterned regions with microbeads attached to the support and the microbeads are modified with at least one functionalizing molecule such that, one molecule member is bound to the microbeads and the other is bound to the molecule of interest, how the functionalizing molecule is attached does not change the resulting microbead. Therefore, any support the support suitable for cell culture, characterized by patterned regions with microbeads attached to the support and the microbeads are modified with at least one functionalizing molecule such that, one molecule member is bound to the microbeads and the other is bound to the molecule of interest, would read on this limitation.
For claim 11, the claim is directed to the support according to claim 10. The support of claim 10 is required to be suitable for cell culture, characterized by patterned regions with microbeads attached to the support and the microbeads are modified with at least one functionalizing molecule, and the patterned regions promote cell adhesion. Claim 11 states that the coating of the support with a compound of composition that promotes cell adhesion is carried out by coating the protrusions of the stamp with said compound or composition that promotes cell adhesion and contacting the support with the stamp thereby allowing the transfer of the compound or composition from the stamp onto the support with a pattern that matches the pattern of protrusions of the stamp. The resulting support is suitable for cell culture, characterized by patterned regions with microbeads attached to the support and the microbeads are modified with at least one functionalizing molecule, and the patterned regions promote cell adhesion. The method by which the support is created still results in the support described above and in claim 10. Therefore, any support is suitable for cell culture, characterized by patterned regions with microbeads attached to the support and the microbeads are modified with at least one functionalizing molecule, and the patterned regions promote cell adhesion, would read on this limitation.
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, 11, 12, and 14 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, 12, and 14 recite the phrase “preferably”. This phrase renders the claim indefinite because it is unclear whether the limitation following the phrase is a part of the claimed invention (See, MPEP 2173.05(d)).
For compact prosecution, limitations recited after ‘preferably’ are not considered to be required by the claim.
Claim 11 recites the limitation "...by coating the protrusions of the stamp with..." in lines 2-3. There is insufficient antecedent basis for this limitation in the claim. The claim is dependent upon claim 10, which is dependent upon claim 1. Neither claim 1 nor claim 10 recite anything about a stamp in regard to the invention. Therefore, there is no stamp to which claim 11 can refer to.
Appropriate correction or clarification is required.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3, 5-8, and 10-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sivagnanam et al (Languir: the ACS journal of surfaces and colloids, 2010) and evidenced by Invitrogen™ Fisher Scientific Dynabeads.
Sivagnanam et al teaches the culturing of MCF-7 breast cancer cells on self-assembled protein coated magnetic beads in a microfluidic chip (See, Abstract).
Regarding claims 1, 2, and 5, Sivagnanam et al teaches streptavidin-coated magnetic beads were patterned inside a sealed microfluidic channel and then were coated with immunospecific cell-capture ligands and cell-adhesion promoting proteins (See, p6092 col 2 paragraph 2). This reads on, a support suitable for culturing cells characterized in that it show patterned regions, said pattern being defined by a complementary pattern of uniformly distributed microbeads attached to the support… of claim 1.
Sivagnanam et al teaches in Figure 1, the beads are patterned on a glass structure of a PDMS microfluidic device. The streptavidin-coated beads are coupled with biotinylated antibodies and fibronectin. The MCF-7 cells are shown to attach and grow on the beads aided by fibronectin and after a few hours of culturing, the biomarker of the antibody is detected on the cell surface of the MCF-7 cells (See, Figure 1, 2 and 4). This reads on, …wherein the microbeads are modified with at least one functionalizing molecule, wherein the pattern regions in the support defined by the microbeads show increased adhesive capacity to cells with respect to the regions to which the microbeads are attached of claim 1.
This also reads on claims 2 and 5, as mentioned above, they are product by process claims and the support that reads on claim 1, reads on the support of claims 2 and 5. Regarding claim 3, following the discussion above, Sivagnanam et al teaches that the streptavidin beads have a diameter of 1.05μm (equal to 1050 nm) (See, p6092 col 2 paragraph 2). This reads on, wherein the diameter of the microbeads is between 50nm to 25000 nm.
Regarding claim 6, following the discussion above, Sivagnanam et al teaches that the streptavidin beads from Invitrogen™, Dynabeads. Dynabeads are polystyrene-based beads covalently coupled with recombinant Streptavidin (See, p6092 col 2 paragraph 2 and Invitrogen™ specification sheet). This reads on, wherein the microbeads are…polystyrene microbeads.
Regarding claims 7 and 8, following the discussion above, Sivagnanam et al teaches the streptavidin-coated beads are coupled with biotinylated 5D10 monoclonal antibody (mAb) and fibronectin (See, Figure 1). As streptavidin-biotinylated molecular coupling is how the microbeads are paired with the molecule of interest; this reads on, wherein the functionalizing molecule... one member of the coupling pair is bound to the microbeads and the other member of the coupling molecular pair is bound to the molecule of interest of claim 7.
This also reads on, wherein the coupling molecule pair is the streptavidin-biotin molecule pair of claim 8.
Regarding claims 10-12, following the discussion above, Sivagnanam et al teaches the microbeads are molecularly coupled with fibronectin, an extracellular cell-adhesion promoting protein (See, Figure 1 and p6092 col 1). This reads on, wherein the patterned regions in the support are coated with a compound or composition that promotes cell adhesion of claim 10.
This also reads on claim 11, as mentioned about the claim is a product by process claim and the support that reads on claim 10, reads on the support of claim 11.
This also reads on, wherein the compound that promotes cell adhesion is an extracellular matrix molecule of claim 12.
Regarding claim 13, following the discussion above, Sivagnanam et al teaches the beads are patterned on a glass structure of a PDMS microfluidic device (See, Figure 1). This reads on, wherein the support is made from a material…glass, as the beads are on glass substrate structure in the microfluidic device.
Regarding claim 14, following the discussion above, Sivagnanam et al teaches that streptavidin coated beads were patterned in the form of 50μm wide stripes with a pitch of 40μm. The beads were arranged to form dots within the stripes with a diameter of 5μm (See, p 6094 col 2 paragraph 2). This reads on, wherein the patterned regions have a geometrical form, as the stripes and dots (circles) are geometric forms or shapes.
Regarding claim 15, following the discussion above, Sivagnanam et al teaches the MCF-7 cells attach and grow on the beads aided by fibronectin and after a few hours of culturing, the biomarker of the antibody is detected on the cell surface of the MCF-7 cells (See, Figure 1, 2 and 4). This reads on, wherein the support further contains viable cells which are attached to the support or to the molecules within the support which promote cell adhesion.
Therefore, claims 1-3, 5-8, and 10-15 are anticipated by Sivagnanam et al and evidenced by Invitrogen™ specification sheet.
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.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Sivagnanam et al (Languir: the ACS journal of surfaces and colloids, 2010) as applied to claims 1-3, 5-15 above, and further in view of Bong et al (Langmuir : the ACS journal of surfaces and colloids, 2015).
The teachings of Sivagnanam et al are set forth above.
Regarding claim 4, following the discussion above, Sivagnanam et al is silent on further coating the regions the microbeads are attached to with a compound or composition which substantially reduces cell adhesion.
Bong et al teaches the attachment of collagen, an extracellular matrix (ECM) material and poly-L-Lysine (PLL), a cell-adhesion promoter, to a hydrogel particle through coupling reaction between amine and N-hydroxysuccinimide (NHS) and streptavidin-biotin conjugation, such that cells attach to the coated particles (See, p2 paragraph 3).
Bong et al teaches the use of microfluidic device made with PDMS partially cured onto a glass slide (See, p3 paragraph 2). Bong et al teaches that the particles were added to a reservoir where the glass bottom and the PDMS walls were coated with poly(ethylene glycol) PEG, an anti-fouling agent. The particles and cells are incubated until the cells attach to the particles (See, p 5 paragraph 3).
As both Sivagnanam et al and Bong et al teach the use of microbeads or particles in cell culturing for cell adhesion. It would have been prima facie obvious to a person having ordinary skill in the art to have modified the support suitable for culturing cells to have the regions where the microbeads are attached to as taught by Sivagnanam et al such that the regions on the support between the patterns of attached microbeads are coated with PEG as taught by Bong et al. As PEG is an anti-fouling agent, it would make it so the cells would not adhere to the non-patterned regions of the support. This conclusion of obviousness is based on teaching suggestion motivation rationale. One would have been motivated to make this modification to the support to further ensure the cells only adhere to the microbeads and not the other regions of the support. One would have had a reasonable expectation of success evidenced by Bong et al.
Therefore, claim 4 is rendered obvious by Sivagnanam et al in view of Bong et al.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Sivagnanam et al (Languir: the ACS journal of surfaces and colloids, 2010) as applied to claim1-3, 5-15 above, and further in view of Morille et al (Journal of controlled release: official journal of the controlled release society, 2013).
The teachings of Sivagnanam et al are set forth above.
Regarding claim 9, Sivagnanam et al teaches the streptavidin-coated beads are coupled with biotinylated 5D10 monoclonal antibody (mAb) and fibronectin (See, Figure 1). While Sivagnanam et al teaches the use of microbeads with two different molecular couplings, it is silent on the use of two different microbeads.
Morille et al teaches the use of biodegradable poly (D,L-lactide-co-glycolide acid) (PLGA) microspheres with added P188 poloxamer covered in fibronectin on the surface to enhance mesenchymal stem cell (MSC) survival and proliferation (See, Abstract).
Morille et al teaches the PLGA microspheres are coated with fibronectin and poly-D-lysine (PDL). The fibronectin surface was characterized by microscopy and immunostaining (See, p 101 col 2 paragraphs 1-2).
Morille et al teaches in Figure 2, that the human MSCs (hMSCs) adhere to the microspheres in culture and form 3D complexes (See, p 104 col 1 paragraph 2, Figure 2).
Given that Sivagnanam et al and Morille et al teach methods of culturing cells with microbeads/spheres with functionalized molecules, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to substitute a portion of the polystyrene microbeads with fibronectin of Sivagnanam et al, with the PLGA microspheres coated with fibronectin, as taught by Morille et al for a similar purpose of cell adhesion.
The substitution of a portion of the microbeads/spheres would result in presence of two types of microbeads. The substitution is a predictable use of prior art elements according to their established functions, leading to predictable results of culturing cells on microbeads/spheres. This rationale aligns with the principle of KSR for simple substitution of one known element for another to obtain predictable results (See, MPEP 2143).
Therefore, claim 9 is rendered obvious by Sivagnanam et al in view of Morille et al.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Caroline M Lara whose telephone number is (571)272-4262. The examiner can normally be reached 7:00 to 4:30pm M-Th.
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/CAROLINE M LARA/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633
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