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 .
DETAILED ACTION
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 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.
Status of the Claims
Claims 23-43 are currently pending.
Claims 23-43 have been considered on the merits.
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they include the following reference character(s) not mentioned in the description: for Fig. 10 there is no description of 304b, 304c, 306a, 306b, 306c, 306d on pg. 25 of the specification and for Fig. 11 there is no description of NO. 400 pg. 27 of the specification.
In addition, the drawings are objected to because of the following informalities: there is description of color in the Specification of Fig. 22B pg. 5 lines 8, Fig. 22C on pg. 5 lines 17-18, and Fig. 24A on pg. 6 line 8 and the various colors cannot be distinguished from each other since the figures are in black and white.
Corrected drawing sheets in compliance with 37 CFR 1.121(d), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR 1.121(b) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities: the use of trademarks.
The use of the terms MitoTracker® on pg. 5 lines 6, 8, and 18; PrestoBlue® on pg. 6 line 24, pg. 32 lines 20, 22-23; Accutase® on pg. 10 line 38; DermLife® K Keratinocyte Medium Complete Kit on pg. 29 line 31; Alexa Fluor® on pg. 31 line 17; Steriflip® filtered on pg. 32 line 13; PicoGreen® fluorescence on pg. 32 line 25; ImageXpress® Micro XLS Imaging System on pg. 32 line 30; GraphPad Prism® on pg. 33 lines 5-6, which are a trade names or a marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
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.
Claim 43 is 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.
In claim 43, lines 1-2, the phrase "the cultivation method enhances the secretory activity of Mesenchymal Stem Cells (MSCs)" lacks sufficient antecedent basis and renders the claim and its dependents indefinite. Claim 23 from which Claim 43 depends from does not have mesenchymal stem cells in the method.
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.
(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 23, 30-31, 34, and 40-43 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Mellot (US 2019/0241849 A1) (ref. of record).
With respect to claim 23 step (i), Mellot teaches providing an interlocking 3D cell culture substrates or expandable cell culture substrates made from hydrogels (an initial scaffolding comprising a first interlocking porous hydrogel block (IPHB)) (0039, 0051, abstract and Fig. 1-6). Mellot teaches the expandable cell culture substrates have voids that form interconnected pores to accommodate cells (the first IPHB comprises a three-dimensional (3D) macrostructure defined by a continuous polymeric matrix material and a network of microporous channels and/or chambers extending throughout the continuous polymeric matrix material) (0041). Mellot teaches the 3D macrostructure comprises a top surface, a bottom surface, and a thickness defined by at least one side edge extending from the top surface to the bottom surface, and wherein the 3D macrostructure structure includes at least one interlocking-male component and at least one interlocking-female component (Figs. 1-6).
With respect to claim 23 step (ii), Mellot teaches the expandable cell culture substrate can be seeded with cells (seeding the first IPHB with one or more cells of interest) (0041 and 0054-0055).
With respect to claim 23 step (iii), Mellot teaches the cells divide within the expandable cel culture substrate and providing solutions to provide nutrients (feeding the one or more cells of interest with a first culture media, and allowing the one or more cells of interest to propagate throughout the network of microporous channels and/or chambers) (0055-0057).
With respect to claim 23 step (iv), Mellot teaches the expandable cell culture substrate where interlocking three dimensional structures are joined together by an interlocking-male component with an interlocking female component (expanding the initial scaffolding by interlocking a second IPHB to the first IPHB, wherein the at least one interlocking-male component or at least one interlocking-female component of the first IPHB is joined to a corresponding interlocking-male component or corresponding interlocking-female component of the second IPHB) (0012, 0032 and Fig. 6).
With respect to claim 23 step (v), Mellot further teaches the method where cells from original expandable cell culture substrate proliferate and migrate into a later coupled expandable cell culture substrate and where the structures are in cell culture medium (allowing the one or more cells of interest to propagate from the first IPHB into the second IPHB, and feeding the one or more cells of interest located inside the second IPHB with the first culture media or a second culture media) (0002, 0008, 0012, 0071-0072 and 0074).
With respect to claim 30, Mellot teaches the method where cells are isolated from the expandable cell culture substrate (harvesting at least a portion of the one or more cells located throughout the network of microporous channels and/or chambers of the first IPHB) (0059 and 0065).
With respect to claim 31, Mellot teaches the method of removing the cells by degrading or dissolving the three-dimensional structure or by using trypsin which would be understood to require flushing the cells out with a fluid medium (harvesting at least a portion of the one or more cells located throughout the network of microporous channels and/or chambers of the first IPHB comprises flushing them out of the first IPHB with a fluid medium or degrading the 3D macrostructure of the first IPHB) (0062).
With respect to claim 34, Mellot teaches the method where cells from different cultures and/or sources can be combined by coupling of expandable cell culture substrates (the method comprises a multi-cell cultivation method, where the one or more cells of interest seeded in the first IPHB comprises a first cell type and the second IPHB is seeded with a second cell type, where the first cell type is different than the second cell type) (0054).
With respect to claims 40 and 41, Mellot teaches the method can be used to produce protein (0065) and teaches the cells can be transfected with a plasmid to produce a heterologous protein (0064).
With respect to claim 42, Mellot teaches the method where the expandable cell culture substrate is coated additional materials to promote cell growth and attachment (coating an interface between the continuous polymeric matrix material and the network of microporous channels and/or chambers extending throughout the continuous polymeric matrix material with a compatibilizer, wherein the compatibilizer is selected to promote adhesion of a primary cell of interest to the IPHB) (0042-0043).
With respect to claim 43, Mellot teaches the method where mesenchymal stem cells are cultured in the substrates (0056).
With respect to the phrase, “wherein the cultivation method enhances the secretory activity of Mesenchymal Stem Cells (MSCs), improving their regenerative potential for therapeutic applications” of the claim, this wherein clause recites an intended result of the method rather than requiring an additional step be performed. MPEP 2111.04 states “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed” and that a such a clause ‘"in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Therefore since these claims only recite the results of the steps, then art reading on claimed method will also read on these results since performing the same steps will inherently lead to the same results in the absence of evidence to the contrary including unexpected results.
Therefore, the reference anticipates the claimed subject matter.
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.
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 23 and 30-43 are rejected under 35 U.S.C. 103 as being unpatentable over Mellot (US 2019/0241849 A1) (ref. of record).
With respect to claim 23 step (i), Mellot teaches providing an interlocking 3D cell culture substrates or expandable cell culture substrates made from hydrogels (an initial scaffolding comprising a first interlocking porous hydrogel block (IPHB)) (0039, 0051, abstract and Fig. 1-6). Mellot teaches the expandable cell culture substrates have voids that form interconnected pores to accommodate cells (the first IPHB comprises a three-dimensional (3D) macrostructure defined by a continuous polymeric matrix material and a network of microporous channels and/or chambers extending throughout the continuous polymeric matrix material) (0041). Mellot teaches the 3D macrostructure comprises a top surface, a bottom surface, and a thickness defined by at least one side edge extending from the top surface to the bottom surface, and wherein the 3D macrostructure structure includes at least one interlocking-male component and at least one interlocking-female component (Figs. 1-6).
With respect to claim 23 step (ii), Mellot teaches the expandable cell culture substrate can be seeded with cells (seeding the first IPHB with one or more cells of interest) (0041 and 0054-0055).
With respect to claim 23 step (iii), Mellot teaches the cells divide within the expandable cel culture substrate and providing solutions to provide nutrients (feeding the one or more cells of interest with a first culture media, and allowing the one or more cells of interest to propagate throughout the network of microporous channels and/or chambers) (0055-0057).
With respect to claim 23 step (iv), Mellot teaches the expandable cell culture substrate where interlocking three dimensional structures are joined together by an interlocking-male component with an interlocking female component (expanding the initial scaffolding by interlocking a second IPHB to the first IPHB, wherein the at least one interlocking-male component or at least one interlocking-female component of the first IPHB is joined to a corresponding interlocking-male component or corresponding interlocking-female component of the second IPHB) (0012, 0032 and Fig. 6).
With respect to claim 23 step (v), Mellot further teaches the method where cells from original expandable cell culture substrate proliferate and migrate into a later coupled expandable cell culture substrate and where the structures are in cell culture medium (allowing the one or more cells of interest to propagate from the first IPHB into the second IPHB, and feeding the one or more cells of interest located inside the second IPHB with the first culture media or a second culture media) (0002, 0008, 0012, 0071-0072 and 0074).
With respect to claim 30, Mellot teaches the method where cells are isolated from the expandable cell culture substrate (harvesting at least a portion of the one or more cells located throughout the network of microporous channels and/or chambers of the first IPHB) (0059 and 0065).
With respect to claim 31, Mellot teaches the method of removing the cells by degrading or dissolving the three-dimensional structure or by using trypsin which would be understood to require flushing the cells out with a fluid medium (harvesting at least a portion of the one or more cells located throughout the network of microporous channels and/or chambers of the first IPHB comprises flushing them out of the first IPHB with a fluid medium or degrading the 3D macrostructure of the first IPHB) (0062).
With respect to claim 32, Mellot teaches the method where the additional expandable cell culture substrates are added to tailor the cell culture conditions based on propagation and/or location of cells (0070-0072). Mellot further teaches the adding of additional units when the cell culture reaches a particular density to increase the surface area of the expandable cell culture surface as needed (abstract, 0036, 0054-0055 and 0065). Based on these teachings of Mellot, it would be obvious to one of ordinary skill in the art to modify the method of Mellot to use chain cultivation where there is the sequential addition of a plurality of secondary blocks to the first IPHB, where the plurality of secondary blocks includes the second IPHB and a third IPHB interconnected directly to the second IPHB such that the second IPHB is located directly between the first IPHB and the third IPHB, and where the plurality of secondary IPHBs are initially devoid of cells as recited in claim 32.
With respect to claim 33, Mellot teaches the method where the expandable cell culture substrates can be removed from the culture and transferred to other vessels (0033 and 0054). Mellot teaches isolating the cells expanded cells from the substrates (0058). Based on these teachings of Mellot, it would be obvious to one of ordinary skill in the art to modify the method of Mellot to harvest the cells of interest located in the first IPHB after cell propagation from the first IPHB to the second IPHB, and to harvest the cells of interest located in the second IPHB after cell propagation from the second IPHB to the third IPHB as recite in claim 33.
With respect to claim 34, Mellot teaches the method where cells from different cultures and/or sources can be combined by coupling of expandable cell culture substrates (the method comprises a multi-cell cultivation method, where the one or more cells of interest seeded in the first IPHB comprises a first cell type and the second IPHB is seeded with a second cell type, where the first cell type is different than the second cell type) (0054).
Mellot does not teach the method where cells of the first cell type and cells of the second cell type are allowed to propagate towards each other and form a first interface between the first cell type and the second cell type as recited in claim 35. Similarly, Mellot does not teach the method further comprising the step of degrading each of the IPHBs to expose each cell type and the first interface as recited in claim 36. Mellot does not teach the method further comprising interlocking a third IPHB directly together with the second IPHB, wherein the second IPHB is located directly between the first IPHB and the third IPHB, and seeding the third IPHB with a third cell type that is different from the first cell type and the second cell type as recited in claim 37. Similarly, Mellot does not teach the method where the cells of the second cell type and cells of the third cell type are allowed to propagate towards each other and form a second interface between the second cell type and the third cell type as recited in claim 38. Likewise, Mellot does not teach the method further comprising a step of degrading each of the IPHBs to expose each cell type, the first interface, and the second interface as recited in claim 39.
However, one of ordinary skill in the art, in view of the common general knowledge would readily recognize that different cell types could be applied to a first, second, or third expandable cell culture substrate structure of Mellot and that the different cells would propagate or expand and meet at an interface. One of ordinary skill in the art would be motivated to use multiple cell types since it common to co-culture different cells. Similarly, one of ordinary skill in the art would have applied the same technique of degrading the cell culture substrate structure to isolate the different cell types and the interfaces formed between them. Furthermore, one of ordinary skill in the art would have had a reasonable expectation of success in making such a modification to Mellot, since co-culturing and the isolating of cells was routinely done.
With respect to claims 40 and 41, Mellot teaches the method can be used to produce protein (0065) and teaches the cells can be transfected with a plasmid to produce a heterologous protein (0064).
With respect to claim 42, Mellot teaches the method where the expandable cell culture substrate is coated additional materials to promote cell growth and attachment (coating an interface between the continuous polymeric matrix material and the network of microporous channels and/or chambers extending throughout the continuous polymeric matrix material with a compatibilizer, wherein the compatibilizer is selected to promote adhesion of a primary cell of interest to the IPHB) (0042-0043).
With respect to claim 43, Mellot teaches the method where mesenchymal stem cells are cultured in the substrates (0056).
With respect to the phrase, “wherein the cultivation method enhances the secretory activity of Mesenchymal Stem Cells (MSCs), improving their regenerative potential for therapeutic applications” of the claim, this wherein clause recites an intended result of the method rather than requiring an additional step be performed. MPEP 2111.04 states “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed” and that a such a clause ‘"in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Therefore since these claims only recite the results of the steps, then art reading on claimed method will also read on these results since performing the same steps will inherently lead to the same results in the absence of evidence to the contrary including unexpected results.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 24-27 and 29 are rejected under 35 U.S.C. 103(a) as being unpatentable over Mellot (as applied to claims 23 and 30-43 above), and further in view of Hinton et al. (Science Advances, 2015).
The teachings of Mellot can be found in the previous rejection above.
Mellot does not teach the various configurations of the microporous channels that are recited in claims 24-27 and 29.
However, Hinton teaches that printed hydrogels can be made containing a variety of different patterns within the gel (abstract and Fig. 2). With respect claim 25, Hinton teaches hydrogels with a spiral pattern (Fig. 2) and teaches hydrogels where the cells adhere to walls of the network of microporous channels and/or chambers (Fig. 3). Based on these teachings, it would be obvious to one of ordinary skill in the art that the spiral patterned channel could be configured so that the cells adhere to the walls of the network of microporous channels and/or chambers. With respect claim 26, Hinton teaches hydrogels with a network of microporous channels and/or chambers and define a network of nodes and branches defining open regions therebetween (Fig. 2 and Fig. 3). With respect claim 27, Hinton teaches hydrogels where one or more cells of interest grow and propagate through the network of microporous channels and/or chambers and define a continuous cell sheet adhered to walls of the network of microporous channels and/or chambers (Fig. 3).
Hinton does not teach the method where the one or more cells of interest wind back-and-forth in a 3D configuration across a portion of individual microporous channels as recited in claim 24. Hinton does not teach the method where the one or more cells of interest grow and propagate through the network of microporous channels and/or chambers and define a comet-like structure having a spheroid structure and a spiral structure emanating from the spheroid structure as the one or more cells of interest propagate from an interior portion of the first IPHB towards one or more exterior surfaces, such as the top surface, the bottom surface, and/or or the at least one side edge as recited in claim 29. However, the skilled person would infer that the microporous channel structures can include cavities or chambers, micropores, channels, tortuous arrangements of channels, substantially straight channels or many different configurations based on the teachings in Hinton.
With respect to the limitation of “as the one or more cells of interest propagate from an interior portion of the first IPHB towards one or more exterior surfaces, such as the top surface, the bottom surface, and/or or the at least one side edge” of claim 24-27 and 29, it would have been obvious one of ordinary skill in art based on the teachings of Hinton that cells would propagate in this direction when seeded in an interior portion of the gel.
Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to modify the method of Mellot, to include hydrogels with various different channel or pore configurations for the benefit of tailoring the hydrogel to the desired shapes needed as taught by Hinton. One of ordinary skill in the art would be motivated to provide channels and/or chambers tailored to the shape and size of the expanding and proliferating cells of interest. Based on the teachings of Hinton, one of ordinary skill in the art would infer that the microporous channel structures can include cavities or chambers, micropores, channels, tortuous arrangements of channels, substantially straight channels or many different configurations based on the teachings in Hinton. The skilled person would find it a minor modification to Mellot to provide the arrangement of winding, spiral, comet-like sheets or a set of nodes branches as disclosed in claims 24-27 and 29. Additionally, one of ordinary skill in the art would have had a reasonable expectation of success in making such a modification to Mellot, since Hinton teaches that hydrogels for cell culture can easily be made with many different channel configurations.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 28 is rejected under 35 U.S.C. 103(a) as being unpatentable over Mellot (as applied to claims 23 and 30-43 above), and further in view of Su et al. (Biosensors, 2021).
The teachings of Mellot can be found in the previous rejection above.
Mellot does not teach the method where the one or more cells of interest grow and propagate through the network of microporous channels and/or chambers and define a spheroid are recited in claim 28.
However, Su teaches hydrogels where the one or more cells of interest grow and propagate through the network of microporous channels and/or chambers and define a spheroid (Fig. 4 and 5, pg. 12 para. 2). Su teaches the spheroid-in-gel-culture has advantages over existing spheroid culture platforms such as simple fabrication, and operation, the ability to preserve the biological complexity and the scalability (pg. 12 last para).
Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to modify the method of Mellot, to include hydrogels where the one or more cells of interest grow and propagate through the network of microporous channels and/or chambers and define a spheroid for the benefit of tailoring the hydrogel to culture spheroid cultures as taught by Su. It would have been obvious to one of ordinary skill in the art to modify Mellot to include additional configurations of the gel so that spheroids could be cultured, since Su teaches hydrogels configured for such purpose. Additionally, one of ordinary skill in the art would have had a reasonable expectation of success in making such a modification to Mellot, since Su teaches that hydrogels for cell culture can be made for culturing spheroids.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp
Claims 23-41 and 43 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 40, 48-49, and 56-57 of copending Application No. 18/726687. Although the conflicting claims are not identical, they are not patentably distinct from each other because the instant claims encompass those of the copending patent application. In addition, both claim methods of culturing cells on interlocking hydrogel blocks.
The limitations of instant claim 23 step (i) are recited by claim 40 step (i) of App. No. 18/726687 of providing an initial scaffolding comprising a first interlocking porous hydrogel block (IPHB), wherein the first IPHB comprises a three-dimensional (3D) macrostructure defined by a continuous polymeric matrix material and a network of microporous channels and/or chambers extending throughout the continuous polymeric matrix material, and wherein the 3D macrostructure comprises a top surface, a bottom surface, and a thickness defined by at least one side edge extending from the top surface to the bottom surface, and wherein the 3D macrostructure structure includes at least one interlocking-male component and at least one interlocking-female component. The limitation of seeding the first IPHB with one or more cells of interest of instant claim 23 step (ii) is recited by claim 40 steps (ii) and (iii) of App. No. 18/726687. The limitation of feeding the one or more cells of interest with a first culture media, and allowing the one or more cells of interest to propagate throughout the network of microporous channels and/or chambers of instant claim 23 step (iii) is recited by claim 40 steps (iv) and (v) of App. No. 18/726687. The limitations of expanding the initial scaffolding by interlocking a second IPHB to the first IPHB, wherein the at least one interlocking-male component or at least one interlocking-female component of the first IPHB is joined to a corresponding interlocking-male component or corresponding interlocking-female component of the second IPHB of instant claim 23 step (iv) are recited by claim 40 step (i) of App. No. 18/726687. The limitation of allowing the one or more cells of interest to propagate from the first IPHB into the second IPHB, and feeding the one or more cells of interest located inside the second IPHB with the first culture media or a second culture media of instant claim 23 step (v) is recited by claim 40 steps (iv) and (v) of App. No. 18/726687.
The claims of App. No. 18/726687 do not recite the limitations of the various configurations of the microporous channels recited in instant claims 24-29. However, one of ordinary skill in the art would readily recognize that the microporous channel structures can include variety of different cavities or chamber, micropores, channels, tortuous arrangements of channels or substantially straight channels. One of ordinary skill in the art would find it a minor modification to the claims of App. No. 18/726687 to provide the arrangement of winding, spiral, spheroid, comet-like sheets or a set of nodes branches as disclosed in instant claims 24-29. The skilled person would be motivated to provide channels and/or chambers tailored to the shape and size of the expanding and proliferating cells of interest.
The limitation of harvesting at least a portion of the one or more cells located throughout the network of microporous channels and/or chambers of the first IPHB of instant claim 30 is recited by claim 49 of App. No. 18/726687.
The limitations of the step of harvesting at least a portion of the one or more cells located throughout the network of microporous channels and/or chambers of the first IPHB comprises flushing them out of the first IPHB with a fluid medium or degrading the 3D macrostructure of the first IPHB of instant claim 31 are recited by claim 56 of App. No. 18/726687.
The claims of App. No. 18/726687 do not recite the limitations of instant claim 32, where the method comprises chain cultivation where there is the sequential addition of a plurality of secondary blocks to the first IPHB, where the plurality of secondary blocks includes the second IPHB and a third IPHB interconnected directly to the second IPHB such that the second IPHB is located directly between the first IPHB and the third IPHB, and where the plurality of secondary IPHBs are initially devoid of cells. However, it would be obvious to one of ordinary skill in the art to modify the method of App. No. 18/726687 to use chain cultivation where there is the sequential addition of IPHB blocks, since claim 40 of App. No. 18/726687 recites a first step of chain cultivation and it would be merely repeating this step multiple times.
Although the claims of App. No. 18/726687 do not recite the limitations of instant claim 33, where the cells of interest located in the first IPHB are harvested after cell propagation from the first IPHB to the second IPHB, and to harvest the cells of interest located in the second IPHB after cell propagation from the second IPHB to the third IPHB. However, it would be obvious to one of ordinary skill in the art to modify the method of App. No. 18/726687 to use chain cultivation where there is the sequential addition of IPHB blocks, since claim 49 of App. No. 18/726687 recites a first step of harvesting the cells from the IPHB blocks and it would be merely repeating this step as the culture expands.
The limitations of the method comprises a multi-cell cultivation method, wherein the one or more cells of interest seeded in the first IPHB comprises a first cell type and the second IPHB is seeded with a second cell type, wherein the first cell type is different than the second cell type of instant claim 34 are recited by claim 40 steps (ii) and (iii) of App. No. 18/726687.
The limitations of the cells of the first cell type and cells of the second cell type are allowed to propagate towards each other and form a first interface between the first cell type and the second cell type of instant claim 35 are recited by claim 40 steps (iv), (v) and (vi) of App. No. 18/726687.
Although the claims of App. No. 18/726687 do not recite the limitations of instant claims 36 and 39, where the method includes a step of degrading each of the IPHBs to expose each cell type and the first interface and a second interface. However, it would be obvious to one of ordinary skill in the art to modify the method of App. No. 18/726687 to include this step, since claim 35 of App. No. 18/726687 recites culturing two cell types and claim 49 recites harvesting the cells. One or ordinary skill in the art would readily recognize that they could apply harvesting to IPHBs with different cell types and multiple interfaces.
The limitations of interlocking a third IPHB directly together with the second IPHB, wherein the second IPHB is located directly between the first IPHB and the third IPHB, and seeding the third IPHB with a third cell type that is different from the first cell type and the second cell type of instant claim 37 are recited by claim 48 of App. No. 18/726687. Although claim 48 of App. No. 18/726687 doesn’t explicitly recite that the second IPHB is located between the first and third IPHB this configuration could easily be conceived by one of ordinary skill in the art.
The limitation of the cells of the second cell type and cells of the third cell type are allowed to propagate towards each other and form a second interface between the second cell type and the third cell type of instant claim 38 is recited by claim 48 of App. No. 18/726687.
The limitation of the one or more cells of interest produce or secrete a therapeutic of interest of instant claim 40 is recited by claim 57 of App. No. 18/726687.
Although the claims of App. No. 18/726687 do not recite that the therapeutic of interest contains exosomes, extracellular vesicles, growth factors, monoclonal antibodies, peptides, proteins, viral particles, oligonucleotides, organelles, or combinations thereof as recited in instant claim 41, these are readily recognized as cell culture products and therapeutics.
With respect to instant claim 43, the phrase, “wherein the cultivation method enhances the secretory activity of Mesenchymal Stem Cells (MSCs), improving their regenerative potential for therapeutic applications” of the claim, this wherein clause recites an intended result of the method rather than requiring an additional step be performed. MPEP 2111.04 states “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed” and that a such a clause ‘"in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Therefore since these claims only recite the results of the steps, then the claims of App. No. 18/726687 which recite the claimed method reads on these results since performing the same steps will inherently lead to the same results in the absence of evidence to the contrary including unexpected results.
Claim 42 is provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 40, 48-49, and 56-57 of copending Application No. 18/726687 and in view of Mellot (US 2019/0241849 A1).
The claims of App. No. 18/726687 do not recite the method where the method includes a step of coating an interface between the continuous polymeric matrix material and the network of microporous channels and/or chambers extending throughout the continuous polymeric matrix material with a compatibilizer, wherein the compatibilizer is selected to promote adhesion of a primary cell of interest to the IPHB as recited in instant claim 42.
However, Mellot teaches the method where the expandable cell culture substrate is coated additional materials to promote cell growth and attachment (coating an interface between the continuous polymeric matrix material and the network of microporous channels and/or chambers extending throughout the continuous polymeric matrix material with a compatibilizer, wherein the compatibilizer is selected to promote adhesion of a primary cell of interest to the IPHB) (0042-0043). Accordingly, it would have been obvious to one of ordinary skill in the art to modify the method of the claims of App. No. 18/726687 to include a step of coating the substrates to promote cell adhesion in the hydrogel, since coatings were known at the time and aided in cell growth and adhesion as taught by Mellot.
Conclusion
No claims are allowed.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Hamilton et al. "Development of 3D hydrogel culture systems with on‐demand cell separation." Biotechnology journal 8.4 (2013): 485-495.
Hamilton teaches providing an interlocking 3D construct made from hydrogel (an initial scaffolding comprising a first interlocking porous hydrogel block (IPHB)) (pg. 487 Col. 2 para. 1, Figs. 2 and 3). However, Hamilton teaches encapsulating the cells in the hydrogels and does not teach a network of microporous channels and/or chambers extending throughout the continuous polymeric matrix material as recited in claim 23 step (i).
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/EMILY A CORDAS/Primary Examiner, Art Unit 1632
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