Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 1-6, 8-10, 12, 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 Claims 72-73, 113, 115, 117, 120, 133, and 139 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 1-6, 8-10, and 12 have been considered on the merits. All arguments have been fully considered.
Status of Rejections
Status of the rejections: The previous claim rejections under 35 USC 112(b) and 112(d) are withdrawn in view of the claim amendments. The non-statutory double patenting rejections in view of 18/0344,55 is withdrawn.
Claim Objections
Claim 1 is objected to because of the following informalities:
In claim 1, the word “herein” appears to be a typographical error for the term “wherein.” Appropriate correction is required.
Claim Interpretation
Claim 1 is interpreted as a product-by-process regarding the phrase “the biocompatible glue is added to the decellularised microchannels during bundling” 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. Similarly, claims 3-5 and 9 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,” “by compressing/packing the microchannels or by fastening the microchannels,” and “used for isolating” 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 12, a “decellularized” microchannel comprising living cells is interpreted as a product-by-process wherein the microchannel is made to be decellularized specifically of plant or fungal cells and then incorporating animal cells because the microchannels of a claimed product having microchannels comprising animal cells cannot be considered decellularized generally.
In claim 1, the phrase “arranged parallel” with regard to the relative positioning of the decellularized microchannels in the bundle(s) 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 substance capable of holding microchannels in place, such as occurring naturally polymers in fungi or 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. It is noted that the term “glue” encompasses a glue that has already set or dried as the claimed invention is a product-by-process made by adding the glue at some point to form part of the scaffold biomaterial, and such glues eventually and ordinarily become intertwined polymers, such as a naturally occurring extracellular matrix substance.
Claim Rejections - 35 USC § 101 (maintained)
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, and 12 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 scaffold biomaterial composition comprising a glue and a bundle of microchannels comprising a plurality of parallel decellularized plant or fungal microchannels wherein the microchannels are bundled together with a biocompatible glue. Note, claims 1, 3-5, 9, and 12 are interpreted as presented in a previous section.
As the claims encompass compositions comprising a nature-based product, i.e., decellularized plant or fungal 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 a biocompatible glue contributing to the stability of the bundle.
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.).
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.). These animals could have climbed onto or in the plant microchannels after the death of all the cells of the microchannels (i.e., due to a natural decellularizing such as decomposition).
The claims thus encompass compositions that are 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 a cellulose and microchannels 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 living plant 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 existing in nature or bundled 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 a process of making the claimed product or what the claimed biomaterial is used for (e.g., see claim 12 “any application,” such as tissue regenerating (treating spinal cord), animal or plant cell scaffold (in replacing/reconstructing a tissue), angiogenesis, filtering, microfluidic, transporting of materials, and/or for promoting plant or animal tissue repair after damage to microvasculature (such as due to disease or an insect). 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 process (e.g., a method of making a scaffold biomaterial).
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.
Response to Arguments
Applicant’s arguments in the response of 6/18/26 (at pg. 7-8) regarding the 101 subject matter eligibility rejections are not found persuasive. Applicant traverses the rejections by arguing the parallel arrangement and the “added” biocompatible glue forming a part of the biomaterial and bundling purposes both provide a markedly different characteristic(s) from any product of nature.
Applicant argues that decaying plant roots or stems progressively lose the parallel arrangement/organization of their microchannels (such as due to loss of cellular matrix, parenchyma and sclerenchyma) as well as lose their structural integrity generally (cohesion) due to degradation. A purported markedly different characteristic of the claimed invention is the presence of a biocompatible glue not subject to such a decay (“e.g., may be substantially non-resorbable or poorly resorbable (i.e. they will not substantially breakdown and be absorbed by the body)” ([0299])). Applicant argues that by the process of making the invention, that naturally occurring biological binding components (including cellular materials, nucleic acids (DNA), proteins) are removed via a decellularization process and the added glue provides for maintenance of the claimed biomaterials structural integrity and parallel microchannel arrangement indefinitely.
As detailed above, it is only the limitations in the claims limiting the claimed product that are examined under 101 and not other aspects such as how the product is made. The presence or absence of natural plant or fungal cohesion factors is not limited by the claims nor is any resistance to biodegradation process required. Importantly, claim 1 encompasses any biocompatible glue, regardless of its degradation properties or whether exogenous to the plant or fungal tissue from which the biomaterial is derived.
While decaying plant stems and roots in nature will eventually lose structural integrity, it is the opinion herein that at early time points there exists in nature plant stems and roots considered both decellularized and comprising a natural biocompatible glue between substantially parallel microchannels as discussed above. It is again emphasized that the claimed invention is a composition (product) and not a method (process), and thus the process steps of “bundling,” “adding” glue and “forming” part of the biomaterial is not considered.
Applicant also argues (pg. 12) that use of a nonnative biocompatible glue in the claimed scaffold biomaterial provides a unique structural permeance and may render the biomaterial " substantially non-resorbable or poorly resorbable" or " resistant to shape change, and/or may hold their intended geometry over long periods of time." However there is no express or implied claim limitation for such feature(s) in any of the instant claims outside of the non-native glue components recited in claim 6. Further, there is no express or implied claim limitation for any densification of the microchannels (greater density) outside of claim 9, which for the 101 analysis must be compared to a decaying tissue instead of the living cellularized tissue from which it was isolated.
Claim Rejections - 35 USC § 112(b), (new)
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 1-6, 8-10, and 12 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.
Claim 1 is directed to a scaffold biomaterial comprising a bundle(s) of isolated, decellularized microchannels and a biocompatible glue added to the decellularized microchannels during bundling, which is incoherent and unclear as to how the microchannels are simultaneously both isolated and in the presence of an added glue according to the ordinary meaning of the term “isolated.” Claims 2-6, 8-10, and 12 are included in this rejection for depending from indefinite claim 1. Moreover, claims 4 and 12 present similar incoherence and lack of clarity for requiring additional added materials like sealants, hydrogels, fasteners, or animal cells within at least one isolated microchannel.
Claim Rejections - 35 USC § 112(d), (new)
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.
Claim 5 is 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.
Claim 5 limits the plurality of decellularized microchannels of claim 1 to be “glued together within the bundle” by a biocompatible glue. However claim 1 already required the plurality of decellularized microchannels be bundled together by a biocompatible glue added during bundling and forming part of the scaffold biomaterial. Thus, claim 5 fails to further limit the subject matter of claim 1 or 4. It is noted that claim 5 allows for but does not require the biocompatible glue to also be biodegradable and/or low-volume.
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, (modified)
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, and 12 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 and extracellular matrices of its ground tissue) (Abstract) and processed to introduce microchannels ([0045]; [0027]; Example 13, [0309]-[0314], FIG. 33-36), wherein the biomaterial comprises a bundle comprising a plurality of microchannels arranged parallel to each other as in nature, 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 claim 12, 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]). Furthermore the intended uses for the claimed product recited in the claim do not imply any structural feature(s) that imply any unrecited structure.
Thus, Pelling anticipates the claimed invention.
Response to Arguments
Applicant’s arguments in the response of 6/18/26 (at pg. 9-10) are not found persuasive. Applicant traverses arguing that Pelling fails to teach isolated microchannels bundled together by a biocompatible glue.
While the Office agrees that a process of making the claimed product may be fundamentally different from any process disclosed in Pelling, the claims are directed to a product, not a process. As noted above, claim 1 is interpreted as a product-by-process regarding the phrases “the biocompatible glue is added to the decellularised microchannels during bundling,” “isolated” or “glued” or bundled “by using sealants,” “by mechanical packing,” “by suspending microchannels in hydrogels,” “by compressing/packing the microchannels or by fastening the microchannels,” and “used for isolating.” When analyzing a product comprising a glue, there is no way to determine how or if the glue was added and nothing in instant claims 1-5, 8-10, and 12 requires the glue to be exogenous or not natively present as argued (e.g., as an externally applied bonding agent).
In Pelling, native, non-cellular, plant structures of the plant holding the tissue together are considered both a “biocompatible glue” and part of the bundle of microchannels satisfying all required functions recited in claim 1 for the glue.
Claim Rejections - 35 USC § 103, (modified)
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 1-6, 8, 10, and 12 are 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, and 12, and thus the subject matter of claims 1-5, 8, 10, and 12 are rendered obvious in view of Pelling.
Regarding claim 6, 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.
Claims 1-5, 8-10, and 12 are 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)).
As set forth fully above, Pelling anticipates claims 1-5, 8, 10, and 12, and thus the subject matter of claims 1-5, 8, 10, and 12 are rendered obvious in view of Pelling.
Regarding claim 9, 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.
Response to Arguments
Applicant’s arguments in the response of 6/18/26 (at pg. 10-12) are not found persuasive. Applicant argues that the prior art fails to teach bundling isolated microchannels together in bundle held together by a biocompatible glue. However the claims are directed to a product not a process of making the product regarding the claim 1 phrases “the biocompatible glue is added to the decellularised microchannels during bundling,” “isolated” or “glued.” When analyzing a product comprising a glue, there is no way to determine why a glue is present (bundling versus tissue adhesive) and nothing in claim 6 precludes the presence of an adhesive glue as argued, including one forming part of the internal structure once set.
Applicant argues a lack of motivation to combine Pelling and Otani and reasonable expectation of success to arrive at a method of making the product comprising deconstruct of a plant tissue and reconstruction into a bundle of isolated decellularized microchannels. Again, claim 6 is directed to a product not a process of making the product. While it is agreed that Pelling and Otani does not teach the purpose of “bundling” the microchannels using the taught gelatin glue or fibrin glue, the combination of Pelling and Otani is determined to teach adding a gelatin/fibrin glue to bundles already held together by a native glue as taught by Pelling wherein the adding comprises the adhesive glue of Otani penetrating into the internal structure of the already structured bundle(s) to provide additional support.
Applicant also argues the claimed product’s properties have superior performance, including being substantially non-resorbable or poorly resorbable (i.e. they will not substantially breakdown and be absorbed by the body)” ([0299])) due to the removal of naturally occurring biological binding components (including cellular materials, nucleic acids (DNA), proteins) via a decellularization process and adding of the glue provides for maintenance of the claimed biomaterials structural integrity and parallel microchannel arrangement over long periods of time due to the added biocompatible glue. However none of these structures or features are clearly required by any limitation in the claims and cannot be inferred merely from the current express recitations, including process steps for making the product-by-process.
Double Patenting, (maintained)
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, and 12 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 biocompatible glue, i.e., a plurality of microchannels arranged parallel to each other and bundled together by the glue making up part of the biomaterial. 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 biocompatible 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 claim 12, 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).
Claims 1-5, 8-10, and 12 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, and 12 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 biocompatible 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 biocompatible 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 claim 12, 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). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-6, 8-10, and 12 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.
Response to Arguments
Applicant’s response (at pg. 12-26, Tables) was not persuasive regarding the claims of US 11,045,582 and 17/611035. These arguments are not found persuasive in part because the claims are directed to a product, not any method of making a product, and thus there is no consideration for any act of “bundling” or “adding” a biocompatible glue to form part of the scaffold matrix or any process resulting in “channel densification.” Instead, the inquiry is whether the product’s structural claim limitations are met in the form of a microchannel bundle and the presence of a biocompatible glue in the bundle regardless of when the glue may or may not have been added to arrive at such a product.
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, such as e.g., the cellulose or chitin in claim 1 of 11,045,582 or other components inherent to the species encompassed by the broad genus of decellularized tissues therein. Furthermore, claim 1 of 17/611,035 clearly requires the presence of a gel, hydrogel glue and/or cross-linking be present to “hold the entire scaffold biomaterial together” (e.g., comprising gelatin, collagen, and/or fibrin).
Applicant also argues the claimed product’s properties have superior performance, including being substantially non-resorbable or poorly resorbable; however as noted above regarding, obviousness none of these structures or features are clearly required by any limitation in the claims and cannot be inferred merely from the current express recitations, including process steps for making the product-by-process.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERIC J ROGERS whose telephone number is (571)272-8338. The examiner can normally be reached Monday - Friday 9:00-6:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached on (571) 272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERIC J ROGERS/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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