Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on Oct. 6, 2025 has been entered.
Claim Status
Claims 1-6, 8-10, 12, 16-17, 72-73, 113, 115, 117, 120, 133, and 139 are currently pending in this application.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-6, 8-10, 12, and 16-17, in the reply filed on Oct. 22, 2024 is acknowledged. Claims 72-73, 113, 115, 117, 120, 133, and 139 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 1-6, 8-10, 12, and 16-17 have been considered on the merits. All arguments have been fully considered.
Claim Interpretation
In claim 1, the term “parallel” with regard to the relative positioning of the decellularized microchannels in the bundle is interpreted as encompassing slight or occasional deviations from strictly parallel regarding each and every microchannel and encompassing intertwined microchannels, such as occurring in nature in plant roots and stems. When viewed in light of the specification the term “parallel” in the phrase “arranged parallel to each other” is always preceded with the qualifier “substantially.” Thus, within the specific context and guidance of the instant application the term “parallel” has been given a scope consistent with the specification. See MPEP 2111.01.
Under a broadest reasonable claim interpretation, the term “glue” in the claims encompasses any adhesive substance capable of holding microchannels in place, such as occurring naturally in plant roots and stems, such as e.g., in the form of biopolymers of heteropolysaccharides (like pectin, cellulose, and hemicellulose), actin, microtubules, septins, and/or clathrins.
Claims 3-5 are each interpreted as a product-by-process regarding the phrases “isolated” or “glued” or bundled “by using sealants,” “by mechanical packing,” “by suspending microchannels in hydrogels” and “by compressing/packing the microchannels or by fastening the microchannels” such that there are no structural feature(s) recited in this claim that would distinguish the claimed scaffold biomaterial product from one made by another process beyond in claim 4 implying the limitation that scaffold biomaterial may comprise a sealant, hydrogel or fastening means, respectively. Claim 4 does not strictly require the final scaffold biomaterial to comprise any sealant, hydrogel, or fastening structure, which could be lost or removed during the process to arrive at a final product.
In claim 9, the phrase “a density of microchannels within the plant or fungal tissue” is interpreted to mean a density of any microchannels in a plant or fungal tissue from at least one of the plant or fungus (e.g., same biological species) from which the microchannels are apparently obtained from, isolated from, or otherwise derived.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-5, 8-10, 12, and 16-17 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claim as a whole, these claims do not recite something significantly different than a judicial exception. The rationale for this determination is explained below.
The claims are directed to:
A biomaterial composition comprising a bundle of microchannels comprising a plurality of parallel decellularized microchannels isolated from plant tissue wherein the microchannels are bundled together with glue.
Thus, the claims are directed to compositions comprising a nature-based product, i.e., decellularized plant tissue material, this nature-based product is analyzed to determine whether it has markedly different characteristics from any naturally occurring counterpart(s) in their natural state. In this regard, scaffold biomaterials comprising a bundle of parallel microchannels exist entirely in nature, including with or without a glue bundling the microchannels together.
Regarding claims 1-3 and 5, the prior art teaches that vascular plant tissues (stems and roots) naturally comprise 3-D vascular bundles comprising a plurality of parallel microchannels, i.e., comprising both a phloem and xylem microchannel (see Lucas et al., J Integr Plant Biol 55: 294-388 (2013) at pg. 301, left col., last para.; Fig. 5A, D; Fig. 11-12). The instant specification teaches that these microchannel bundles can be obtained and isolated directly from natural plant tissues and decellularized, e.g., from asparagus or celery tissue (Examples 1-3). Alternatively, the prior art teaches vascular plant tissue may become decellularized during natural decay or upon death, such as due to parasitism (Yoshida et al., Annu Rev Plant Biol 67: 643-7 (2016) at Fig. 3-4). Further, the prior art teaches plant stem tissues comprise a plurality of parallel phloem and xylem naturally arranged in an overall 3-D vascular bundle (Lucas at Fig. 5, 11-12) that is held together by a natural biocompatible “glue” (biopolymers and extracellular matrix) particularly comprising cellulose and/or lignin as commonly seen in woody plants (id. at pg. 320, left col., 1st para.; Fig. 12).
Regarding claim 4, the prior art teaches plant stem tissues comprise a plurality of parallel phloem and xylem naturally arranged in an overall 3-D vascular bundle that is held together in part by hydrogels, including extracellular matrix and cell wall biopolymers particularly comprising cellulose and/or lignin (Lucas at pg. 320, left col., 1st para.; Fig. 12), xylem pit membranes (id. at pg. 332, left col., 2nd para.), and other pectin and lignin structures, which enhance the strength of the stem (Pelling at [0286]).
Regarding claim 8, the art teaches vascular plant stems comprise cellulose and lignin (pg. 309, right col., last para.), particularly in the cell walls of the phloem and xylem vasculature (Lucas at pg. 304, left col., 2nd para.; pg. 310, right col., 1st para.).
Claim is interpreted as presented in a previous section. Regarding claim 9, a cross-section of naturally occurring phloem microchannels from a given species of plant’s distal twig is denser than the xylem microchannels of the trunk from the same species (see e.g., Jyske and Holtta, New Phytol 205: 102-15 (2015) at Table 1).
Regarding claim 10, Lucas discloses these structures are present in flowering plants of Brassicaceae (e.g., Arabidopsis) (pg. 321), thus the natural features described above are present in stem and root tissues of Brasscia rapa and Brassica oleracea.
Regarding claim 12, the art teaches vascular plant tissue may comprise living animal cells in the form of larvae and nematodes living on or within their root and stem microchannels, such as larvae of the Asparagus moth Parahypopta caestrum (El Khoury et al., Biocontrol Science and Technology 30: 983-95 (2020) at pg. 2, 2nd para.).
The claims thus encompass a composition that is identical (no difference in characteristics) to naturally occurring compositions comprising vascular plant stem tissue lacking cells or that has been intentionally decellularized. A dead or decaying plant stem may become decellularized yet leaving behind the cellulose bundle structure encompassed by the claims. Further, there is no evidence that a process of isolation and decellularizing and/or gluing microchannels thereof into bundles substantially changes a vascular plant root or stem tissue beyond removal of all living cells.
Because there is no difference between the bundle used in the claims and naturally occurring plant vascular bundles having cells or naturally decellularized, the claimed biomaterial do not have markedly different characteristics, and thus are a “product of nature” exception. In re Roslin Institute (Edinburgh), 750 F.3d 1333, 1338-39 (Fed. Cir. 2014). Accordingly, the claimed invention is directed to an exception. Because the claimed invention does not include any additional features that could add significantly more to the exception, the claimed culture does not qualify as eligible subject matter, and should be rejected under 35 U.S.C. § 101 as explained below.
An examination of Step 2A in the revised 101 guidance, with respect to the claimed invention, the answer is yes because the claimed invention comprises naturally occurring products, in the instant case these naturally occurring products are certain plant tissues or bundle biomaterials derived from such plant tissues. When examining the claimed invention with regards to Step 2A prong 1, the answer is yes because the claimed invention comprises naturally occurring products. When examining the claimed invention with regards to Step 2A prong 2, the answer is no since the claimed invention does not integrate the judicial exception, in the instant case a scaffold biomaterial, into a practical application.
It is only the recited limitations in the claims that are examined under 101 and not aspects such as what the composition is used for (e.g., transporting of materials, animal cell scaffold, or for promoting tissue repair, regeneration, or angiogenesis). In this case, only biomaterial compositions comprising a glued bundle of microchannels comprising a plurality of parallel decellularized microchannels isolated from plant tissue are examined with respect to their status as judicial exceptions. It is emphasized that the claimed invention is a composition and not a method.
An examination of Step 2B, the answer is no with respect to the claimed invention. There are no other additional elements recited in the claim that would amount to significantly more than the judicial exceptions. The compositions as claimed are indistinguishable from those that exist in nature and there are no limitations that add any additional elements to the claimed compositions. The bundle of microchannels have the same overall structure, shape and arrangement as in nature and the fact that they may exist in an isolated form lacking cells (decellularized) does not appear to change the bundle in significant or meaningful way to amount to more than the judicial exception.
Regarding claims 16-17, the recited intended use limitations do not limit the claim with any implied structure/function not positively recited in the claim, so claims 16-17 do not add any markedly different characteristic, integrate the product into a practical application or amount to significantly more than the judicial exception. The only factors which can be examined under 101 in the claimed composition are those that are recited in the claims, i.e. the scaffold biomaterial structure. How the product is obtained (e.g., by “gluing”) and possible product uses are not considered with respect to a composition claim, as it is only the judicial exceptions themselves that are analyzed under 101.
Response to Arguments
Applicant’s arguments (at pg. 7-8) regarding the 101 subject matter eligibility rejections are not found persuasive. Applicant traverses the rejections by arguing both the parallel arrangement of the microchannels in the bundle, even if entangled in 3D, and the presence of a glue for bundling purposes provide a markedly different characteristic(s) from any product of nature.
As detailed above, it is only the limitations in the claims limiting the claimed product that are examined under 101 and not aspects such as how the product is made. In this case, only biomaterial compositions comprising a glued bundle of microchannels comprising a plurality of parallel decellularized microchannels isolated from plant tissue are examined with respect to their status as judicial exceptions. It is again emphasized that the claimed invention is a composition (product) and not a method (process), and thus the process step of “gluing” is not considered.
Applicant also traverses the rejections (pg. 8) by arguing the bundle comprising a combination of vascular tissue from different areas of different plants, such as those not naturally found in parallel arrangements also provide a markedly different characteristic(s) from any product of nature. However there is no express or implied claim limitation for such a feature(s) in any of the instant claims.
Applicant argues (pg. 8) that the microchannels in the bundle can have a higher density than the naturally occurring tissue they’re isolated from; however this argument is only applicable to claim 9. Applicant is reminded that claims 1 and 9 are directed to a product and not a process of making a product (e.g., comprising isolating, decellularizing, bundling and gluing microchannels). In claim 9, the limitation “a density of microchannels within the plant or fungal tissue” is ambiguous as to which tissue(s) to use for the comparison when the plant and/or fungal tissue(s) from which the microchannels are obtained from is not always clear when presented with manipulated bundles of isolated and decellularized microchannels from one or more plants and/or fungus for use in identification of the natural source(s) for comparison. If the comparison is to the same species of plant or fungus at an uncertain tissue location (e.g., stem/trunk proximal or distal to the root), then the exact tissue used in the comparison can alter the result (greater or ≤) so claim 9 encompass naturally occurring counterparts. Furthermore, if the microchannels are derived from a plurality of tissues or species, then a single species or specific tissue thereof used in the comparison can alter the result to encompass naturally occurring bundles of microchannels as noted above regarding the density of some isolated xylem channels encompassed by the claims compared to some naturally occurring bundles of more dense phloem channels from the same species of plant, or at different tissue locations thereof.
Claim Rejections - 35 USC § 112(b)
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 4-6 and 9 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 pre-AIA the applicant regards as the invention.
The claims are interpreted as provided in a previous section.
Claim 4 recites the term “compressing/packing,” which is not clear if what is before and after the slash forms a single limitation, recites an optional feature, or alternative limitations. Claims 5-6 are included in this rejection for being dependent, either directly or indirectly, on indefinite claim 4.
In claim 9, the phrase “a density of microchannels within the plant or fungal tissue” is ambiguous and unclear as to which tissue to use for the comparison when the plant or fungal tissue from which the microchannels are obtained from is not always clear when only presented with manipulated bundles of isolated and decellularized microchannels for use in their identification. Furthermore, plants comprise different types of microchannels, such as phloem and xylem, and thus the phrase encompasses wherein the density of phloem of a plant tissue is less than a decellularized bundle of xylem channels from the same tissue. In addition, a density of any microchannels within the plant or fungus’s tissues can vary greatly due to whether living or dead, hydrated or desiccated, lacking sap, fossilized, etc. Thusly, a person skilled in the art would not understands the metes and bounds of “the density of microchannels within the plant or fungal tissue” with regard to a scaffold biomaterial comprising a bundle of decellularized microchannels isolated from at least one plant or fungal tissue. For example, in Applicant’s remarks of May 6, 2025, applicant submits that the bundle may comprise microchannels from different areas of different plants (pg. 8).
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 16-17 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Each of claims 16 and 17 further recites only language regarding what the biomaterial of claim 1 “is for”, but none of these intended uses implies any additional structure/feature to the biomaterial that is not in already inherent to the scaffold biomaterial of claim 1. Thus, both of these dependent claims fails to further limit the subject matter of a claim upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 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.
(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 1-5, 8, 10, 12, and 16-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pelling (US 20190060520 A1; priority to 2017-02-10).
Regarding claim 1, Pelling discloses a decellularized scaffold biomaterial comprising a porous decellularized plant or fungal tissue held together by a biocompatible glue (e.g., cellulose) (Abstract) processed to introduce microchannels ([0045]; [0027]; Example 13, [0309]-[0314], FIG. 33-36) and wherein the biomaterial comprises a bundle comprising a plurality of microchannels arranged parallel to each other, e.g., derived from an asparagus tissue (FIG. 33A-B; 34A).
Regarding claim 2, Pelling discloses the plurality of microchannels arranged parallel to each other are xylem structures (Example 13; FIG. 33A and 34A, [0108]-[0109]).
Regarding claim 3, Pelling discloses wherein the decellularized xylem channels are grouped in a vascular bundle isolated from a plant (id.; [0311], FIG. 34B).
Pelling anticipates claims 4 and 5 by virtue of anticipating claim 1 as set forth fully above because there are no structural feature(s) recited or implied in every alternative in these claim that would distinguish the claimed scaffold biomaterial product from one made by another process.
Regarding claim 8, Pelling discloses an asparagus-based decellularized scaffold biomaterial comprises cellulose ([0248]).
Regarding instant claim 10, Pelling discloses deriving the biomaterial specifically from an asparagus stem tissue (e.g., from Asparagus officinalis) ([0029]; [0103]).
Regarding claims 12 and 16, Pelling discloses growing non-native cells (primary rat neurospheres) on the asparagus-derived scaffold (Example 13, [0310]-[0311], FIG. 34) for use in implanted grafts to repair or regenerate tissue in a spinal cord injury ([0174-[0175]) comprising vascular injury (T8 severance) ([0311]).
Regarding claims 16-17, Pelling discloses the biomaterial may be used as a biocompatible scaffold for supporting animal cell growth, promoting tissue regeneration, treatment/repair of spinal cord injury, and repair of animal tissue, such as tissue comprising damaged microvasculature (spinal cord damage from T8 severance) (id.). Furthermore for applying prior art, an intended use of a claimed product only limits the claim if there is an implied structure not recited in the claims (see Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999) as “it is important not to import into a claim limitations that are not part of the claim.” See MPEP 2111.01.02. Claim 16 and 17 are both interpreted with an implied limitation to wherein the scaffold biomaterial is biocompatible for the intended uses of: “treatment and/or repair of spinal cord injury;” “repair or reconstruction or replacement of plant or animal tissue;” “any suitable application in which biocompatible micrometer-scale channels may be of use;” and “repair or reconstruction or replacement of plant or animal tissue, wherein the plant or animal tissue comprises damaged microvasculature, or plant tissue damaged by vascular disease, or damaged vascular structure of trees infested with an insect.” At least one of the alternative uses in each of claims 16 and 17 is satisfied by a decellularized scaffold biomaterial disclosed by Pelling by virtue of disclosing all the required structures of the biomaterial of claim 1.
Thus, Pelling anticipates the claimed invention.
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.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Pelling (US 20190060520 A1; priority to 2017-02-10) in view of Otani (Otani et al., Biomaterials 17: 1387-91 (1996)).
As set forth fully above, Pelling anticipates claims 1-5, 8, 10, 12, and 16-17, and thus the subject matter of claims 1-5, 8, 10, 12, and 16-17 is rendered obvious in view of Pelling.
Pelling does not teach wherein a glue component of the scaffold biomaterial holding the bundle together specifically comprises gelatin or fibrin.
However Otani teaches adhesive glues comprising fibrin (conventional fibrin glue) or gelatin (gelatin-PLGA).
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to make a decellularized plant or fungal tissue comprising a plurality of microchannels arranged parallel to each other (e.g., of an asparagus vascular tissue(s)) as taught by Pelling wherein a biological glue is added to hold the microchannel construct in place, such as wherein the glue is the gelatin comprising glue taught by Otani. One of ordinary skill in the art would be motivated by Otani to select the gelatin glue (10,000 mg/ml Gel with 100 mg/mL PLGA) that was superior to conventional fibrin glue in terms of bonding strength to living tissues, viscosity for ease of application, speed of curing (pg. 1390, left col., last para., to right col.). Furthermore, one with the goal of using such a scaffold derived from asparagus tissue for use as a bioimplant as taught by Pelling ([0248]; Example 13) would be motivated to use gluing to ensure the stability of the entire construct before implantation into a subject.
Thus, the claimed invention as a whole is prima facie obvious to one of ordinary skill in the art before the effective time of filing in the absence of evidence to the contrary.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Pelling (US 20190060520 A1; priority to 2017-02-10) in view of Adamski (Adamski et al., J Vis Exp 135: e57586 (2018)) as evidenced by Derome (Derome et al., Phil. Mag. 92: 3680-98 (2012)).
Pelling does not teach the decellularized scaffold biomaterial comprises a greater density of microchannels than within the plant tissue it was derived from.
However Adamski teaches storing decellularized plant tissues by lyophilization or freeze-drying various (pg. 2, Protocols 1 and 2, #4(1) and pg. 3, #3: “lyophilize…”) wherein the intended use of the decellularized biomaterial is for tissue engineering applications due to, e.g., their excellent water transport ability, wide availability, low cost, and biocompatibility (Abstract).
Derome teaches drying plant tissue results in shrinking, such as due to changes in cell wall components such as cellulose (Abstract; Fig. 2, 12).
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to lyophilize the biomaterial of Pelling as taught by Adamski for convenient storage, which inherently causes the density of the structures to increase relative to plant tissues in their natural state (whether cellular or acellular) as evidenced by Derome.
Thus, the claimed invention as a whole is prima facie obvious to one of ordinary skill in the art before the effective time of filing 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 conflicting claims 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) 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 www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-5, 8, 10, 12, and 16-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 6 of the “reference patent” US Patent 11,045,582 in view of Pelling and as evidenced by Lucas (Lucas et al., J Integr Plant Biol 55: 294-388 (2013)).
The claims are interpreted as set forth in a previous section. Claim 6 of the reference patent is directed to a method of making a three-dimensional decellularized plant or fungal tissue comprising microchannels and which may also comprise a cell growth factor and/or a cell differentiation factor (promoting cell-specificity).
The claims in the instant application differ from the claims of the reference patent in that there must be a bundle and a glue, i.e., a plurality of microchannels arranged parallel to each other and bundled together by a glue. However plant tissues (e.g., asparagus tissues) inherently comprise bundles each having a plurality of microchannels arranged substantially parallel to each other as evidenced by Pelling (Example 13; FIG. 33A and 34A, [0108]-[0109]) and a glue connecting the microchannels together (cell wall biopolymers and extracellular matrix), particularly comprising cellulose and/or lignin as evidenced by Lucas (pg. 320, left col., 1st para.; Fig. 12).
It would have been prima facie obvious to one of ordinary skill in the art to perform the method of reference claim 6 to produce a decellularized bundle comprising a plurality of microchannels arranged parallel to each other from an asparagus tissue as taught by Pelling and inherently comprising a natural biocompatible glue connecting the microchannels together (cell wall biopolymers and extracellular matrix) as evidenced by Lucas. One of ordinary skill in the art would have been motivated to choose asparagus-based microchannel materials as scaffolds because Pelling teaches such cellulose-based scaffolds derived from asparagus have already been tested in preclinical trials for use as bioimplants ([0248]; Example 13) and inherently have pectin and lignin structures which enhance the strength of the biomaterial compared to other plant tissue options ([0286]; FIG. 22).
Regarding instant claim 2, Pelling teaches the plurality of microchannels arranged parallel to each other are xylem structures (Example 13; FIG. 33A and 34A, [0108]-[0109]). Regarding instant claim 3, Pelling teaches wherein the decellularized xylem channels are grouped in a vascular bundle isolated from an asparagus plant tissue (id.; [0311], FIG. 34B).
Regarding instant claim 4, Pelling teaches wherein the scaffold biomaterial is made with mechanical packing or by crosslinking (compressed and/or in a cross-linked form), e.g., when the scaffold biomaterial comprises a cellulose-based tissue containing carboxymethylcellulose ([0128]). It would have been prima facie obvious to one of ordinary skill in the art to cross-link the entire asparagus derived biomaterial and the microchannels therein. One of ordinary skill in the art would have been motivated to support the underlying architecture of the natural plant stem tissue as taught by Pelling ([0127]), such as for use as an implant and/or scaffold for mammalian cells ([0310]-[0311], [0174-[0175]).
Regarding instant claim 5, Pelling teaches asparagus tissues with microchannels inherently comprising a biocompatible glue connecting the microchannels together (cell wall biopolymers and extracellular matrix) as evidenced by Lucas (Fig. 5, 11-12). Regarding instant claim 8, reference claim 6 via reference claim 1 teaches wherein the decellularized tissue comprises cellulose and Pelling teaches asparagus-based scaffolds inherently comprise cellulose ([0248]). Regarding instant claim 10, Pelling teaches deriving the biomaterial specifically from an asparagus stem tissue (e.g., from Asparagus officinalis) ([0029]; [0103]).
Regarding instant claims 12 and 16, although the reference claim does not expressly teach wherein non-native living cells are intentionally added to the microchannels, reference claim 6 teaches functionalizing the decellularized tissue with factors commonly used for supporting growth of exogenous animal cells within a material as a scaffold, e.g., a collagen, cell growth factor, and/or a cell differentiation factor. Furthermore, Pelling teaches growing primary rat neurospheres on the asparagus-derived cellulose scaffold (Example 13, FIG. 34) as well as fibroblasts on a plant derived decellularized cellulose scaffold functionalized with collagen (Example 12).
Regarding instant claim 16, it would have been prima facie obvious to one of ordinary skill in the art to use the decellularized bundle produced by reference claim 6 as a biocompatible scaffold for growth of an animal cell on the bundled microchannels, such as fibroblasts in view of Pelling (Example 12).
Furthermore the intended uses for the claimed product recited in claims 16-17 (e.g., wherein the scaffold biomaterial is for repair or reconstruction or replacement of plant or animal tissue) do not imply any structural feature(s) that would distinguish the claimed scaffold biomaterial from ones made by other processes. Thus, the subject matter of claims 16-17 is not patentably distinct from the reference claim(s) in view of Pelling as evidenced by Lucas by virtue of the same reasons set forth for fully above for instant claim 1.
Claims 1-5, 8-10, 12, and 16-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 6 of the “reference patent” US Patent 11,045,582 in view of Pelling and Adamski as evidenced by Lucas and Derome.
Regarding instant claim 9, Adamski teaches storing decellularized plant tissues by lyophilization or freeze-drying various (pg. 2, Protocols 1 and 2, #4(1) and pg. 3, #3: “lyophilize…”) wherein the intended use of the decellularized biomaterial is for tissue engineering applications due to, e.g., their excellent water transport ability, wide availability, low cost, and biocompatibility (Abstract). Furthermore, Derome teaches drying plant tissue inherently results in shrinking, such as due to changes in cell wall components such as cellulose (Abstract; Fig. 2, 12).
It would have been prima facie obvious to one of ordinary skill in the art to lyophilize the plant biomaterial taught by reference claim 6 and Pelling for convenient storage as taught by Adamski, which inherently causes the density of the structures to increase relative to plant tissues in their natural state (whether cellular or acellular) as evidenced by Derome.
Claims 1-6, 8, 10, 12, and 16-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 11, 23-24, and 41 of US 17/611035 (the reference application) in view of Pelling as evidenced by Lucas.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims in the reference application are directed to a decellularized 3D porous scaffold biomaterial derived from a plant or fungal tissue comprising two or more subunits held together with a hydrogel glue, such as for uses involving supporting seeded cells (claim 11) or as an implant for repair or regeneration (claim 41).
The instant claims differ from the reference claims in that the biomaterial must comprise a bundle comprising a plurality of decellularized microchannels arranged parallel with each other and bundled together with a glue. However plant tissues (e.g., asparagus tissues) inherently comprise bundles each having a plurality of microchannels arranged substantially parallel to each other as evidenced by Pelling (Example 13; FIG. 33A and 34A, [0108]-[0109]) and a glue connecting the microchannels together (cell wall biopolymers and extracellular matrix), particularly comprising cellulose and/or lignin as evidenced by Lucas (pg. 320, left col., 1st para.; Fig. 12).
It would have been prima facie obvious to one of ordinary skill in the art to produce the aligned decellularized microchannel bundle of reference claim 1 from asparagus tissue as taught by Pelling. One of ordinary skill in the art would have been motivated to choose asparagus-based materials because Pelling teaches asparagus-based scaffolds have already been tested in preclinical trials for use as bioimplants ([0248]; Example 13) and inherently have pectin and lignin structures which enhance the strength of the biomaterial compared to other plant tissue options ([0286]; FIG. 22).
Regarding instant claim 2, Pelling teaches the plurality of microchannels arranged parallel to each other are xylem structures (Example 13; FIG. 33A and 34A, [0108]-[0109]). Regarding instant claim 3, Pelling teaches wherein the decellularized xylem channels are grouped in a vascular bundle isolated from an asparagus plant tissue (id.; [0311], FIG. 34B).
Regarding instant claims 4-6, reference claim 3 teaches holding biomaterial subunits together with a hydrogel glue comprising gelatin, fibrin, or PEG. Thus, it would have been prima facie obvious to one of ordinary skill in the art to produce the aligned decellularized microchannel bundle of reference claim 1 from asparagus tissue as taught by Pelling with a gluing step using a glue comprising gelatin, fibrin, or PEG to hold the entire scaffold structure together long-term, including the microchannels in the bundle. One of ordinary skill in the art would have been motivated to choose such a glue for biocompatibility during implantation as Pelling teaches asparagus-based scaffolds for use as bioimplants and retaining implant biostructure over a duration of weeks ([0248]; Example 13, [0311], FIG. 34B).
Regarding instant claim 8, reference claim 24 teaches wherein the material is hemicellulose-based or lignin-based, and Pelling teaches asparagus-based scaffolds comprise cellulose and lignin ([0248]; [0097]l [0286]; FIG. 22). Regarding instant claim 10, Pelling teaches deriving the biomaterial specifically from an asparagus stem tissue (e.g., from Asparagus officinalis) ([0029]; [0103]).
Regarding instant claims 12 and 16, reference claims 11 and 41 teach growing living animal cells (e.g., a bone tissue cells) on the scaffold, either in vitro or in vivo. Furthermore, Pelling teaches growing primary rat neurospheres on an asparagus-derived cellulose scaffold (Example 13, FIG. 34). Regarding instant claim 16, it would have been prima facie obvious to one of ordinary skill in the art to use the scaffold of reference claim 1 as a biocompatible scaffold for supporting growth of an animal tissue, such as a population of bone cells taught by reference claim 41 while repairing bone or a wound of a vertebrate, either seeded before implantation or migrating into the scaffold after implantation.
Regarding instant claim 16, Pelling teaches the scaffold biomaterial may be used for supporting animal cell growth, promoting tissue regeneration, treatment and/or repair of spinal cord injury, repair of animal tissue in applications such as growing non-native cells (primary rat neurospheres) on the asparagus-derived scaffold (Example 13, [0310]-[0311], FIG. 34) for use in implanted grafts to repair or regenerate tissue in a spinal cord injury ([0174-[0175]).
Regarding instant claim 17, reference claim 41 teaches scaffold biomaterial uses include for wound healing, tissue repair or regeneration; for providing an implant; for culturing one or more cell types; for mimicking an in vivo tissue or tissue interface; for repair or regeneration of bone; for transporting a fluid or liquid; or any combination thereof. Furthermore, Pelling discloses the asparagus tissue derived scaffold specifically for use in repair of animal tissue comprising damaged microvasculature (spinal cord damage from T8 severance) (Example 13, [0311], FIG. 34).
Furthermore the intended uses for the claimed product recited in claims 16-17 (e.g., wherein the scaffold biomaterial is for repair or reconstruction or replacement of plant or animal tissue) do not imply any structural feature(s) that would distinguish the claimed scaffold biomaterial from ones made by other processes. Thus, the subject matter of claims 16-17 is not patentably distinct from the reference claim(s) in view of Pelling as evidenced by Lucas by virtue of the same reasons set forth for full above for instant claim 1. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-6, 8-10, 12, and 16-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 11, 23-24, and 41 of US 17/611035 (the reference application) in view of Pelling and Adamski as evidenced by Derome and Lucas.
Regarding instant claim 9, Adamski teaches storing decellularized plant tissues by lyophilization or freeze-drying various (pg. 2, Protocols 1 and 2, #4(1) and pg. 3, #3: “lyophilize…”) wherein the intended use of the decellularized biomaterial is for tissue engineering applications due to, e.g., their excellent water transport ability, wide availability, low cost, and biocompatibility (Abstract). Furthermore, Derome teaches drying plant tissue inherently results in shrinking, such as due to changes in cell wall components such as cellulose (Abstract; Fig. 2, 12).
It would have been prima facie obvious to one of ordinary skill in the art for convenient storage to lyophilize as taught by Adamski the biomaterial taught by the combination of the reference claims and Pelling, which inherently causes the density of the structures to increase relative to plant tissues in their natural state (whether cellular or acellular) as evidenced by Derome. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 4-5, 8, 10, 12, and 16-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims claim 10, 56, and 61 of US 18/034455 (the reference application) in view of Pelling and as evidenced by Lucas.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims in the reference application are directed to a decellularized 3-dimensional structure derived from a plant or fungal tissue comprising aligned microchannels, such as for use as a food product (claim 61), cell scaffold (claim 61), or an implant to align growing nerve cells in a subject (claim 56).
The instant claims differ from the reference claims in that the biomaterial must comprise a bundle comprising a plurality of decellularized microchannels arranged parallel with each other and bundled together by a glue.
However Pelling teaches an asparagus plant tissue inherently comprises a xylem bundle having a plurality of microchannels arranged substantially parallel to each other (Example 13; FIG. 33A and 34A, [0108]-[0109]) and natural glue connecting the microchannels together (cell wall biopolymers and extracellular matrix), particularly comprising cellulose and/or lignin as evidenced by Lucas at pg. 320, left col., 1st para.; Fig. 12). Further, Pelling teaches that decellularized asparagus tissue scaffolds have already been tested in preclinical trials for use as bioimplants ([0248]; Example 13) and inherently have pectin and lignin structures which enhance the strength of the biomaterial compared to alternative plant tissue scaffolds ([0286]; FIG. 22).
It would have been prima facie obvious to one of ordinary skill in the art to produce the aligned decellularized microchannel bundle of reference claim 10 from asparagus tissue as taught by Pelling. One of ordinary skill in the art would have been motivated to choose asparagus-based materials because Pelling teaches asparagus-based scaffolds have already been tested in preclinical trials for use as bioimplants ([0248]; Example 13) and inherently have a natural glue as well as pectin and lignin structures which enhance the strength of the biomaterial compared to other plant tissue options ([0286]; FIG. 22).
Regarding instant claim 2, Pelling teaches the plurality of microchannels arranged substantially parallel to each other are xylem structures (Example 13; FIG. 33A and 34A, [0108]-[0109]). Regarding instant claim 3, Pelling teaches wherein the decellularized xylem channels are grouped in a vascular bundle isolated from an asparagus plant tissue (id.; [0311], FIG. 34B).
Regarding instant claim 4, Pelling teaches wherein the scaffold biomaterial is compressed and/or in a cross-linked form (e.g., when the scaffold biomaterial comprises a cellulose-based tissue containing carboxymethylcellulose) ([0128]). It would have been prima facie obvious to one of ordinary skill in the art to cross-link the entire asparagus derived biomaterial and the microchannels therein. One of ordinary skill in the art would have been motivated to support the underlying architecture of the natural plant stem tissue as taught by Pelling ([0127]), such as for use as an implant and/or scaffold for mammalian cells ([0310]-[0311], [0174-[0175]).
Regarding instant claim 5, Pelling teaches asparagus tissues with microchannels inherently comprising a natural biocompatible glue connecting the microchannels together (cell wall biopolymers and extracellular matrix) as evidenced by Lucas (Fig. 5, 11-12). Regarding instant claim 8, Pelling teaches asparagus-based scaffolds inherently comprise cellulose ([0248]). Regarding instant claim 10, Pelling teaches deriving the biomaterial specifically from an asparagus stem tissue (e.g., from Asparagus officinalis) ([0029]; [0103]).
Regarding instant claims 12 and 16, reference claim 56 teaches growing living animal nerve cells on the scaffold and reference claim 61 teaches seeding non-native animal cells, including muscle cells, fibroblasts, neurons, stem cells, adipocytes, etc., with the cells aligned along the parallel microchannels. Furthermore, Pelling teaches growing primary rat neurospheres on an asparagus-derived cellulose scaffold (Example 13, FIG. 34). Regarding instant claim 16, it would have been prima facie obvious to one of ordinary skill in the art to use the decellularized material of reference claim 1 as a biocompatible scaffold for supporting growth of an animal or plant cell, such as an animal cell listed above as taught by reference claim 56 or 61.
Regarding instant claim 17, reference claim 56 teaches uses of the biomaterial include as an implant to align growing nerve cells in a subject. Furthermore, Pelling discloses the asparagus tissue derived scaffold specifically for use in repair of tissue comprising damaged microvasculature (spinal cord damage from T8 severance) (Example 13, [0311], FIG. 34).
Furthermore the intended uses for the claimed product recited in claims 16-17 (e.g., wherein the scaffold biomaterial is for repair or reconstruction or replacement of plant or animal tissue) do not imply any structural feature(s) that would distinguish the claimed scaffold biomaterial from ones made by other processes. Thus, the subject matter of claims 16-17 is not patentably distinct from the reference claim(s) in view of Pelling as evidenced by Lucas by virtue of the same reasons set forth for full above for instant claim 1. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 4-5, 8-10, 12, and 16-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10, 56, and 61 of US 18/034455 (the reference application) in view of Pelling and Adamski as evidenced by Derome and Lucas.
Regarding instant claim 9, Adamski teaches storing decellularized plant tissues by lyophilization or freeze-drying various (pg. 2, Protocols 1 and 2, #4(1) and pg. 3, #3: “lyophilize…”) wherein the intended use of the decellularized biomaterial is for tissue engineering applications due to, e.g., their excellent water transport ability, wide availability, low cost, and biocompatibility (Abstract). Furthermore, Derome teaches drying plant tissue inherently results in shrinking, such as due to changes in cell wall components such as cellulose (Abstract; Fig. 2, 12).
It would have been prima facie obvious to one of ordinary skill in the art for convenient storage to lyophilize as taught by Adamski the biomaterial taught by the combination of the reference claims and Pelling, which inherently causes the density of the structures to increase relative to plant tissues in their natural state (whether cellular or acellular) as evidenced by Derome.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant’s response (at pg. 13) did not provide any specific additional argument beyond the rebuttal of the prior art rejections relying on Pelling, Lucas, Adamski, and/or Derome at pg. 11-13. These arguments are not found persuasive.
As set forth above, there is not any requirement for a gluing step in the claimed product but rather the scaffold biomaterial comprises a “glue” as forming a part of the materials. In addition, the claim limitations of a glue encompass inherent materials present in natural plant stems and roots without any modification.
Conclusion
No claim is allowed.
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/ERIC J ROGERS/Examiner, Art Unit 1638
/KEVIN K HILL/Primary Examiner, Art Unit 1638