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 .
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f):
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f). The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f). The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f), except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f), except as otherwise indicated in an Office action.
Such claim limitations are:
“means for supplying a cell culture medium” which read on one or more of the pumps, ports, fluid lines, valves shown in Figures 1A and 2, as well as other art-recognized equivalents
Claim Objections
Claim 8 is objected to because of the following informalities: the term “imagining element” should be written as “imaging element”. Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 and 5-9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Smith (US 8492140).
With respect to claim 1, Smith discloses a bioreactor adapted for visualizing a tissue sample. Smith teaches that a culture chamber (Figure 10:300) is adapted to receive a tissue sample (Figure 12:310). A fluid inlet port (Figure 10:302) is provided to supply a cell culture medium to the cell culture chamber so as to immerse the tissue sample. This is described in column 17, lines 4-60. A fiber optic imaging element (Figure 12:324) is integrated with the cell culture chamber and is adapted to visualize the culture chamber under in situ conditions. See column 18, lines 38-57 and claim 38 (“system additionally comprises one or more cameras and/or optical probes for the visualization and/or image capture of one or more of fluids, cells, and tissues”).
With respect to claim 5, Smith discloses the apparatus as described above. Smith further teaches in column 21, line 65 to column 22, line 33 that an electromagnetic shaker is used to agitate or shake the cell culture chamber.
With respect to claim 6, Smith discloses the apparatus as described above. Smith additionally states in column 11, lines 16-28 that the bioreactor is adapted to test drug candidates on a tissue sample.
With respect to claim 7, Smith discloses the apparatus as described above. Smith shows that the bioreactor is integrated on a microchip (Figure 5:118).
With respect to claims 8 and 9, Smith discloses the apparatus as described above. The Smith fiber-optic imaging element is “adapted to” visualize, in real time, the tissue sample and provide both bright-field visualization and fluorescent visualization.
Claims 1-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al “Homogeneous Distribution of Exogenous Cells onto De-epithelialized Rat Trachea via Instillation of Cell-Loaded Hydrogel” (cited in the 5/31/2024 IDS).
With respect to claims 1-9, Chen discloses a bioreactor for visualization of a tissue sample comprising means for supplying a cell culture medium and a fiber-optic imaging element (“GRIN lens imaging probe”). This is shown in Figs. 1 and 3. The bioreactor is adapted for receiving a lung tissue sample (e.g., rat trachea) and includes an electromagnetic shaker. The bioreactor is adapted to test drug candidates and is integrated on a microchip (see Fig. 1). Furthermore, the fiber-optic imaging element is adapted to visualize the sample in real time, in both bright-field visualization and fluorescent visualization. See Fig. 4.
With respect to claims 10-20, Chen discloses a method for deepithelializing a tissue sample by immersing the tissue sample in a cell culture medium, interfacing the tissue sample with a detergent (e.g., SDS), mechanically vibrating the tissue sample, washing the tissue sample (e.g., with PBS), delivering a cell loaded hydrogel to the tissue sample, and growing new cells on the tissue sample. See pages B and C. The sample is visualized using a fiber-optic imaging element. Chen states that the tissue sample is a rat lung tissue obtained comprising epithelium cells, and that the new cells may be human MSCs derived from adipose tissue. New cells are seeded using a cell loaded hydrogel comprising a collagen pre-gel having a concentration of 3 mg/mL (“collagen pregel with a 3 mg/mL concentration provided the most uniform particle distribution”).
Claim Rejections - 35 USC § 103
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.
Claims 2 and 3 are rejected under 35 U.S.C. 103 as being unpatentable over Smith (US 8492140) as applied to claim 1, and further in view of Zenhausern (US 20240344022).
Smith discloses the apparatus as described above. Smith further shows in at least Fig. 14 that the tissue sample 310 has a generally cylindrical configuration. Smith, however, does not expressly state that the culture chamber is adapted to receive a lung tissue sample.
Zenhausern discloses a bioreactor for processing a tissue sample comprising a culture chamber (Figure 1A:40) and a means (Figure 1C:6) for supplying a cell culture medium. Zenhausern states that lung tissue samples are decellularized and repopulated by seeding lung epithelial A5-549 cells onto the scaffolds. See paragraphs [0066]-[0080].
Before the effective filing date of the claimed invention, it would have been obvious to use the Smith bioreactor to study and manipulate lung tissue samples. Zenhausern states that it is desirable to evaluate lung tissue in simulated microenvironments to investigate changes in cellular growth, behavior, differentiation, etc. It would have been useful to examine all tissue types in the Smith bioreactor, especially in view of Zenhausern, which notes that “the use of porous 3D scaffolds to provide a suitable environment for the generation of tissues and organs is vital for the exploration of novel cellular models for biomedical research”.
In the alternative, it is noted that the claims do not positively recite the lung tissue sample and tubular configuration, and that the Smith bioreactor “is adapted to” support essentially any tissue type.
Claims 4 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Smith (US 8492140) as applied to claim 1, and further in view of Stasevich (US 20200102373).
Smith discloses the bioreactor as described above. Although Smith teaches that the fiber-optic imaging element is in communication with a CCD camera, Smith does not specifically recite the claimed optical elements.
Stasevich discloses a method for live-cell imaging. Stasevich states in paragraph [0322] that an optical element capable of obtaining dual-edge super-resolution imaging is provided, wherein the optical element includes a camera, an achromatic doublet, a filter lens, a dichroic mirror and an objective lens. Stasevich notes in paragraph [0190] that live cell imaging techniques may use bright field visualization and fluorescent visualization.
Before the effective filing date of the claimed invention, it would have been obvious to use the optical elements taught by Stasevich to image tissue samples in real time when operating the Smith system. As evidenced by Stasevich, each of the claimed elements – camera, achromatic doublet, filter lens, dichroic mirror, objective lens – are known in the art and provide a predictable and useful function. Stasevich shows how this combination of optical elements allows one to obtain live-cell imaging in real time. It is prima facie obvious to apply a known technique to a known device ready for improvement to yield predictable results. See MPEP 2143.
Claims 10, 11 and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over McFetridge (US 20140287451) in view of Radisic (US 20210380950).
With respect to claim 10, McFetridge discloses a method of deepithelializing a tissue sample comprising immersing a tissue sample in a culture medium (“Cells were maintained in VascuLife basal medium supplemented with VEGF LifeFactors kit (LifeLine Cell Technologies; Frederick, Md.) and 100 U/mL penicillin/streptomycin (HyClone; Logan, Utah) at 37°C with 5% CO2”). The tissue sample is interfaced with an aqueous solution of detergent and mechanically vibrated (“Veins were then decellularized by immersion in 1% (w/v) solution of sodium dodecyl sulfate (SDS) in DI water under orbital shaking (100 RPM) for 24 hours at a 1:20 mass to volume ratio”). McFetridge teaches that the tissue sample is washed with a washing solution (“Scaffolds were rinsed for 5 minutes, 15 minutes, 40 minutes, and 1 hour in DI water, and pH balanced in PBS (pH 7.40) for 24 hours”). Endothelial cells are then delivered to the tissue sample and allowed to grow on the tissue sample (“Endothelial cell suspensions (106 cells/mL) were inoculated into the flow field and allowed to settle, attach, and spread out on the scaffold surface for 5 hours”). This is taught in paragraphs [0061]-[0068]. This is accomplished using the flow device shown in Fig. 1.2. McFetridge, however, does not expressly state that the endothelial cells are delivered to the decellularized tissue sample as a cell loaded hydrogel.
Radisic discloses a tissue generation method in which cells are cultured using a collagen hydrogel matrix. This is described throughout the reference, including in paragraphs [0174]-[0179] and [0211]-[0228] and Figure 1A.
Before the effective filing date of the claimed invention, it would have been obvious to deliver a cell loaded hydrogel to the McFetridge tissue sample. Radisic teaches that collagen is an important component of ECMs because it promotes cell adhesion and growth. Those of ordinary skill would understand that collagen hydrogels would improve artificial tissue engineering in a bioreactor by more accurately representing in vivo conditions. It is prima facie obvious to apply a known technique to a known device ready for improvement to yield predictable results. See MPEP 2143.
With respect to claim 11, McFetridge and Radisic disclose the combination as described above. McFetridge further states that tissues and cells are visualized through a viewing window (Figure 1.1:14).
With respect to claim 16, McFetridge and Radisic disclose the combination as described above. McFetridge teaches that the detergent is sodium dodecyl sulfate (SDS).
With respect to claim 17, McFetridge and Radisic disclose the combination as described above. It would have been obvious to conduct the shaking/vibrating step in the McFetridge method at a frequency (e.g., 20 Hz) that is optimized based on art-recognized parameters, such as culture duration, cell type, media volume, and hydrogel composition.
With respect to claim 18, McFetridge and Radisic disclose the combination as described above. McFetridge states that the washing solution may include phosphate buffered saline (PBS).
With respect to claims 19 and 20, McFetridge and Radisic disclose the combination as described above. Radisic further states that the cell loaded hydrogel may be a collagen pre-gel having a concentration of 3 mg/mL. See, for example, paragraph [0277].
Claims 12-15 are rejected under 35 U.S.C. 103 as being unpatentable over McFetridge (US 20140287451) in view of Radisic (US 20210380950) as applied to claim 10, and further in view of Kim (US 20130344490).
McFetridge and Radisic disclose the combination as described above, however do not expressly state that the tissue sample is rat lung tissue or that the new cells are human cells.
Kim discloses a method for deepithelializing a tissue sample. The tissue sample is harvested and immersed in a cell culture medium. A detergent is used to solubilize cells and produce a decellularized biomatrix. See paragraphs [0070]-[0074]. The decellularized matrix is then seeded with human neoplastic cells. At least paragraph [0005] indicates that the tissue sample may include lung epithelial cells obtained from a rat, and that the neoplastic cells are human cells.
Before the effective filing date of the claimed invention, it would have been obvious to use the McFetridge method to evaluate and grow human neoplastic cells supported on decellularized biomatrices comprising lung tissue. Kim discusses the importance of cancer research and highlights the importance of creating tumor models for the study and identification of anti-cancer agents. See paragraphs [0049]-[0058] (“some aspects of this disclosure are based on the surprising discovery that neoplastic cells can form 3D tumor structures reminiscent of in vivo tumor tissue when cultured within a biomatrix from a different species”; “the generation of decellularized biomatrices from mammalian tissue, for example, from rat lung,… [and] [s]eeding of decellularized biomatrices with lung cancer cells led to the generation of lung tumor constructs that closely replicated human lung cancer biology…[t]he described lung cancer constructs and the methods and reagents for their generation described herein, accordingly, provide a new avenue to better understand lung cancer biology”).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATHAN ANDREW BOWERS whose telephone number is (571)272-8613. The examiner can normally be reached M-F 7am-5pm.
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/NATHAN A BOWERS/Primary Examiner, Art Unit 1799