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 .
Status of the Claims
Claims 1-20 are pending (claim set as filed on 08/16/2023).
Priority
This application filed on 08/16/2023 has a PRO 63/403,592 filed on 09/02/2022.
Information Disclosure Statement
The Information Disclosure Statements (IDS) submitted on 01/11/2024 and 06/10/2024 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the Examiner.
Drawings
The drawings filed on 08/16/2023 have been accepted.
Claim Rejections - 35 USC §102, Anticipation
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)(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 1-20 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Jones (US Patent no. 12,043,823 B2 with an effectively filed date of 03/23/2022).
Jones’ general disclosure relates to isolating and expanding living cells, in particular, toward isolating target cells using a membrane and expanding the isolated cells (see abstract & col. 1, lines 26-29).
Regarding base claims 1 and 17, Jones teaches methods of expanding target cells that may be collected from a mixed cell population (see col. 1-2, lines 66-2). Jones teaches “the membrane may be arranged in any form, such as a flat sheet, a filter matrix, a hollow fiber, any combination thereof, and/or any plurality thereof” (see col. 2, lines 32-34).
Regarding claims 2-3 pertaining to the biotinylated molecule, Jones teaches “examples of a secondary coating material may include a soluble protein moiety, biotinylated molecules, an anti-biotin antibody, a biotin-binding and/or streptavidin-binding peptide, a streptavidin, an avidin, monoclonal antibodies, aptamers (e.g., aptamers targeted toward specific cell surface markers), cytokines (e.g., Interleukin (IL)-6, IL-21), chemokines (e.g., stromal cell-derived factor (SDF)-1), equivalents and/or combinations thereof” (see col. 18, lines 43-51).
Regarding claims 4 and 18 pertaining to the ECM component, Jones teaches “examples of a first coating material may include fibronectin, vitronectin, any extracellular matrix (ECM) glycoprotein, collagen, enzyme, equivalents and/or combinations thereof, and/or any molecule or material that is capable of providing cellular adhesion to a membrane or other surface” (see col. 18, lines 37-43).
Regarding claims 5-12 and 19-20 pertaining to the ECM-streptavidin, Jones teaches “the membrane may comprise one or more layers or coatings (i.e., a membrane) that are configured to attract and collect target cells … the first coating material may be fibronectin, or a fibronectin equivalent, and the second coating material may be a soluble protein moiety” (see col. 2, lines 12-25). Jones teaches the “hollow fibers may include a coating on at least one of the lumen surface and the extra-capillary surface of the hollow fibers. The coating may include at least one of streptavidin, avidin, a biotinylated molecule, and an anti-biotin antibody or a functional fragment thereof” (see col. 3, lines 25-33, & col. 18, lines 25-43). Jones further teaches “the covalent coupling of fibronectin to streptavidin, using a similar mass ratio as outlined above, may be achieved using a streptavidin conjugation kit. This kit may make use of a specific linkage modifier and quencher chemistry to generate a covalent linkage between fibronectin and streptavidin in a time period of 30 minutes to 24 hours, and in some implementations in a time period of 3 hours to 15 hours … the coupling of streptavidin-biotinylated molecules to fibronectin using a molar ratio, for example, of 1:3 (fibronectin:streptavidin) may be useful” (see col. 22, lines 10-63).
Regarding claims 13 and 20 pertaining to washing, Jones teaches target species (such as cells) may adhere to the surface(s) of the membrane and non-target species (such as cells or cellular debris) may be washed from the membrane leaving target species contained on the membrane (see col. 18, lines 10-14).
Regarding claim 14 pertaining to the targeted cells, Jones teaches “these target cells may include, but are not limited to, stem cells, CD34+ HSCs, T-cells, natural killer (NK) cells, monocytes, or the like” (see col. 2, lines 10-12).
Regarding claims 11 and 15-16 pertaining to the surface, Jones teaches the hollow fibers of the bioreactor each comprise an interior lumen and an extra-capillary side (see col. 2-3, lines 52-24).
Claim Rejections - 35 USC §103, Obviousness
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 non-obviousness.
Claims 1-2, 4-8, 11-13, 15, 17-18, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Ling (US 2020/0157483 A1 - cited in the IDS filed on 01/11/2024).
Ling’s general disclosure relates to the design, fabrication and applications of three-dimensional (3D) bioreactors for cell expansion and cell secreted substance production (see abstract & ¶ [0002]).
Ling discloses a method for functionalizing a bioreactor for cell expansion of targeted cells (a method of functionalizing a 3D bioreactor by coating it with ECM proteins for target cell expansion (see abstract & ¶ [0045]-[0046], [0086]-[0088]), the method comprising: contacting a biotinylating molecule to a surface of the bioreactor including an extracellular matrix component (the hydrophobic internal surfaces of the bioreactor are coated with a polydopamine primer coating combined with additional layers comprising extracellular matrix proteins and streptavidin, which binds to biotinylated antibodies (see ¶ [0086]-[0088], [0096], [0102]-[0103]), the biotinylating molecule binding to the extracellular matrix component and having an affinity for the targeted cells (biotinylated antibodies, such as anti-CD3 antibodies, bind to the ECM-streptavidin surface and capture T cells (targeted cells) (see ¶ [0086]-[0088], [0096], [0102]-[0103]).
Although Ling does not teach a specific embodiment with the claim’s limitation of a hollow-fiber membrane, Ling does mention a hollow-fiber membrane (a hollow-fiber bioreactor which intrinsically comprises a hollow-fiber membrane (see ¶ [0071], [0078]). Thus, it would have nonetheless been readily obvious to a person of ordinary skill in the art to have modified the method of Ling for the integration of a hollow-fiber membrane, based on the teachings of the alternative embodiment of Ling, as this modification would provide the capability of functionalizing a hollow-fiber membrane bioreactor by coating its surface with ECM-streptavidin and a biotinylated antibody layer to capture and expand target cells, such as T cells, thereby providing an improved hollow-fiber membrane bioreactor for target cell expansion.
Regarding claims 2 and 17, Ling further discloses wherein the biotinylated molecule is selected from the group consisting of: cytokine, epitope, ligand, monoclonal antibody (biotinylated antibodies, such as anti-CD3 antibodies, which encompasses monoclonal antibody, bind to the ECM-streptavidin surface and capture T cells (see ¶ [0086]-[0088], [0096], [0102]-[0103]), stains, aptamer, and combinations thereof.
Regarding claims 4 and 18 pertaining to the ECM component, Ling teaches “For the 3D printed bioreactor (FIG. 7d) using ABS or PMMA, the hydrophobic internal surfaces of the bioreactor are preferably modified to allow for cell adherence. Polydopamine was used as a primer coating to the bioreactor surfaces so that other proteins can be easily adhere to the bioreactor surface via the polydopamine coating. It therefore can be noted that the polydopamine primer coating can be combined with other coatings such as peptides, collagen, fibronectin, laminin, multiple cell extracellular matrix proteins or selected antibodies that are required by particular cell types” (see ¶ [0086]).
Regarding claim 5 pertaining to the ECM component-streptavidin conjugation, Ling further discloses wherein the extracellular matrix component includes an extracellular matrix component-streptavidin conjugation, the extracellular matrix component of the extracellular matrix component-streptavidin conjugation binding to the surface of the bioreactor, and the streptavidin of the extracellular matrix component-streptavidin conjugation binding to the biotinylated molecule (the hydrophobic internal surfaces of the bioreactor are coated with a polydopamine primer coating combined with additional layers comprising extracellular-matrix proteins and streptavidin (ECM component-streptavidin conjugation, the extracellular matrix component binding to the surface of the bioreactor), which binds to biotinylated antibodies (the streptavidin binding to the biotinylated molecule) (see ¶ [0086]-[0088], [0095]-[0096], [0102]-[0103]). As noted above with respect to the hollow-fiber membrane, it would have been obvious to have modified the method, as previously disclosed by Ling, for the integration of a hollow-fiber membrane, based on the teachings of the alternative embodiment of Ling, as this modification would provide the capability of functionalizing a hollow-fiber membrane bioreactor by coating its surface with ECM-streptavidin and a biotinylated antibody layer to capture and expand target cells, such as T cells, thereby providing an improved hollow-fiber membrane bioreactor for target cell expansion.
Regarding claim 6, Ling discloses a protein-streptavidin conjugation having a mass ratio of the protein to the streptavidin of greater than or equal to about 1:3 (antibodies at a concentration of 10 microgram/ml were captured by a coating layer comprising 30 microgram/ml streptavidin, which translates to a protein-streptavidin conjugation having a mass ratio protein to streptavidin of 1:3; ¶ [0099], [0101]-[0102]). It would have been obvious to have modified the method, as previously disclosed by Ling, for the integration of a protein-streptavidin conjugation having a mass ratio of the protein to the streptavidin of 1:3, based on the teachings of the alternative embodiment of Ling, as this modification would provide the capability of functionalizing a bioreactor by coating its surface with ECM-streptavidin and a biotinylated antibody layer to capture and expand target cells, wherein the ECM-streptavidin conjugation has a well-defined mass ratio, thereby providing an improved bioreactor functionalization method for target cell expansion.
Regarding claims 7-8, Ling further discloses wherein the extracellular matrix component-streptavidin conjugation includes a fibronectin-streptavidin conjugation, the fibronectin having a molecular weight greater than or equal to about 440 kDa to less than or equal to about 500 kDa, and the streptavidin having-a molecular weight greater than or equal to about 53 kDa to less than or equal to about 55 kDa (the hydrophobic internal surfaces of the bioreactor are coated with a polydopamine primer coating combined with additional layers comprising fibronectin and streptavidin, wherein the molecular weights of fibronectin and streptavidin are about 440 kDa and about 53-55 kDa, respectively (see ¶[0086]-[0088], [0096], [0102]-[0103]).
Regarding claims 11-13 and 20, Ling teaches wherein the extracellular matrix component is contacted with the surface of the bioreactor for a period greater than or equal to about 4 hours to less than or equal to about 24 hours prior to the contacting of the biotinylating molecule to the surface (the bioreactor surfaces are first coated by polydopamine, followed by additional layers of fibronectin and streptavidin, wherein the bioreactor is immersed into the coating solution for 12 hours (prior to the contacting of the biotinylating molecule to the surface); the bioreactor is immersed into the coating solution for 12 hours and then washed with PBS prior to the contacting of the biotinylated antibodies (biotinylating molecule) to the surface (see ¶ [0086], [0096], [0099], [0107]). Thus, it would have been obvious to perform washing off any excess and unreacted conjugation components prior to contact with a biotinylated antibody layer to capture and expand target cells, such as T cells, thereby providing an improved hollow-fiber membrane bioreactor for target cell expansion.
Regarding claim 15, Ling teaches wherein the surface is an interior-facing surface (the hydrophobic internal surfaces of the bioreactor are preferably modified to allow for- cell adherence (see ¶ [0086], [0102], [0107]).
Claims 3 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Ling as applied to claims 1-2, 4-8, 11-13, 15, 17-18, and 20 above, and in view of Li (Expansion of NK cells from PBMCs using immobilized 4-1BBL and interleukin-21, 2015 - cited in the IDS filed on 01/11/2024).
Ling’s disclosure is discussed above as it pertains to a method for functionalizing a hollow-fiber membrane for cell expansion.
However, Ling does not teach: wherein the cytokine includes interleukin-21 (claim 3); or wherein the targeted cells include natural killer cells (claim 14).
Li teaches biotinylated IL-21 was bound to streptavidin-labeled Dynabeads, which were used to stimulate human PBMCs, achieving natural killer cell expansion (see abstract, & see page 336, 1st col. 1st ¶).
It would have been obvious to a person of ordinary skill in the art to have modified the method of Ling for the integration of the biotinylated cytokine IL-21, based on the-teachings of Li, as this modification would provide the capability of functionalizing a bioreactor by coating its surface with ECM-streptavidin followed by contact with a biotinylated cytokine IL-21 layer to capture, stimulate, and expand target cells, such as NK cells, thereby providing an improved bioreactor for selective NK cell expansion. It would have been further obvious to employ or substitute the natural killer cells such as taught by Li in the method of Ling as it would be deemed a simple substitution of one known element for another.
Claims 9 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Ling as applied to claims 1-2, 4-8, 11-13, 15, 17-18, and 20 above, and in view of Callahan (US 2016/0143852 A1 - cited in the IDS filed on 01/11/2024).
Ling’s disclosure is discussed above as it pertains to a method for functionalizing a hollow-fiber membrane for cell expansion.
However, Ling does not teach: the preparing of the fibronectin-streptavidin conjugation includes reconstituting lyophilized fibronectin with streptavidin by immerging the lyophilized fibronectin and streptavidin in water (claims 9 and 19).
Callahan discloses preparing of peptide-streptavidin conjugation that-includes reconstituting lyophilized peptide with streptavidin by immerging the lyophilized peptide and streptavidin in water (lyophilized peptibody conjugated with streptavidin, wherein the lyophilized peptide is reconstituted by adding water, which encompasses immerging the lyophilized peptide and streptavidin in water (see abstract & ¶ [0176], [0282]-[0283]).
It would have been obvious to a person of ordinary skill in the art to have modified the method, as previously disclosed by Ling, for the integration of preparing of peptide-streptavidin conjugation that includes reconstituting lyophilized peptide with streptavidin by immerging the lyophilized peptide and streptavidin in water, based on the teachings of Callahan, as this modification would provide the capability of functionalizing a bioreactor by coating its surface with fibronectin-streptavidin followed by contact with a biotinylated molecule that can capture target cells, wherein lyophilized fibronectin is reconstituted with streptavidin using water, thereby providing an improved method for forming the fibronectin-streptavidin conjugate layer and an improved bioreactor functionalization method for selective target cell expansion.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Ling as applied to claims 1-2, 4-8, 11-13, 15, 17-18, and 20 above, and in view of Regev (US 2021/0171938 A1 - cited in the IDS filed on 01/11/2024).
Ling’s disclosure is discussed above as it pertains to a method for functionalizing a hollow-fiber membrane for cell expansion.
However, Ling does not teach: wherein the preparing of the fibronectin-streptavidin conjugation includes covalently coupling the fibronectin and the streptavidin (claim 10).
Regev discloses preparing a protein-streptavidin conjugation that includes covalently coupling the protein and the streptavidin (antibodies are conjugated with streptavidin using the LYNX Rapid Streptavidin Antibody Conjugation Kit, which intrinsically results in covalent coupling between the antibody (protein) and the streptavidin (see ¶ [0078]).
It would have been obvious to a person of ordinary skill in the art to have modified the method of Ling for the integration of preparing a protein-streptavidin conjugation that includes covalently coupling the protein and the streptavidin, based on the teachings of Regev, as this modification would provide the capability of functionalizing a bioreactor by coating its surface with fibronectin-streptavidin followed by contact with a biotinylated molecule that can capture target cells, wherein the fibronectin and streptavidin can be covalently coupled using a streptavidin conjugation kit resulting in a more stable coating layer, thereby providing an improved method for forming the fibronectin-streptavidin conjugate layer and an improved bioreactor functionalization method for selective target cell expansion.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Ling as applied to claims 1-2, 4-8, 11-13, 15, 17-18, and 20 above, and in view of Pinxteren (US 2017/0022472 A1 - cited in the IDS filed on 01/11/2024).
Ling’s disclosure is discussed above as it pertains to a method for functionalizing a hollow-fiber membrane for cell expansion.
However, Ling does not teach: wherein the surface is an exterior-facing surface or a combination of an interior-facing surface and the exterior-facing surface (claim 16).
Pinxteren discloses wherein the surface is an exterior-facing surface or a combination of an interior-facing surface and the exterior-facing surface (extracellular matrix proteins may be
attached to the internal and/or external surface of the fibers of hollow fiber bioreactors (see abstract & ¶ [0052]).
It would have been obvious to a person of ordinary skill in the art to have modified the method of Ling for the integration of wherein the surface is an exterior-facing surface or a combination of an interior-facing surface and the exterior-facing surface, based on the teachings of Pinxteren, as this modification would provide the capability of functionalizing a bioreactor by coating its interior- and exterior-facing surfaces with ECM-streptavidin followed by contact with a biotinylated molecule that can capture target cells, thereby providing a greater surface area for target cell expansion and hence, providing an improved method for bioreactor functionalization for selective target cell expansion.
Conclusion
No claims were allowed.
Correspondence Information
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/NGHI V NGUYEN/Primary Examiner, Art Unit 1653