DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The instant claims herein are examined utilizing the accepted effective filing date of 9/3/2020 for the basis of any prior art rejections.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 recites “a step of . . .; and a step of . . . ” the examiner suggests removing these recitation.
Appropriate correction is required.
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 5-7, 8-11, and 14 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 5 (which recites “when obtaining the mixture, a polyelectrolyte is furthermore mixed with the cells in addition to the cationic substance and the fragmented extracellular matrix to incorporate the polyelectrolyte into the mixture.”) and claim 8 (which recites “when obtaining the mixture, an extracellular matrix component is furthermore mixed with the cells simultaneously or separately with respect to the cationic substance and/or the fragmented extracellular matrix”) are generally narrative and indefinite, failing to conform with current U.S. practice. They appear to be a literal translation into English from a foreign document and are replete with grammatical and idiomatic errors. Thus, the claims are indefinite. Claim 6-7 and 9-11 are included in this rejection for being dependent on indefinite claims 5 and 8 respectively.
Claim 14 recites “[in the equation, X1 represents a thickness of the three-dimensional tissue body after 4 days of culture, and Xo represents a thickness of the three-dimensional tissue body at the start of culture].”. The use of parentheses renders the claims indefinite because it is unclear whether the limitations within the parentheses are part of the claimed invention. It is suggested that the parentheses be removed and the claim is amended to recite, for example, “wherein X1 is a thickness of the three-dimensional tissue body after 4 days of culture; and X0 is the thickness of the three-dimensional tissue body at the start of culture.”
Claim 14 recites “wherein a thickness retention rate represented by an equation below is 80% or higher.” See Application of Collier, 397 F.2d 1003 (C.C.P.A. 1968), which states claims are considered indefinite when “things which may be done are not required to be done". Specifically, it is unclear whether the equation as claimed is required to practice the instant invention. Thus, the claim is indefinite.
It is noted that any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to rejections made based on said interpretations. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office action.
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.
First Rejection – Product of Nature
Claim 12 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (natural product) without significantly more. This judicial exception is not integrated into a practical application and does not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below:
Claim interpretation: Under the broadest reasonable interpretation (BRI), the terms of the claims are presumed to have their plain meaning consistent with the specification as it would be interpreted by one of ordinary skill in the art (see MPEP 2111). Claim 12 recites “three-dimensional tissue body comprising: cells; a fragmented extracellular matrix component; and a polyelectrolyte”. The cells encompass multitude of cells (fibroblasts, epithelial cells, endothelial cells, etc.) , the fragmented extracellular matrix component encompasses fragmented collagen, and polyelectrolyte encompasses polyelectrolytes found in the body (such as, e.g., DNA).
Step 1 (Statutory Category): This part of the eligibility analysis evaluates whether the claim falls within any statutory category. Here, the claims recite a three-dimensional tissue body. This is a composition of matter; therefore, the claims fall within a statutory category. [Step 1: YES]
Step 2A (Judicial Exceptions), Prong 1: This part of the eligibility analysis evaluates whether the claim recites a judicial exception. A claim “recites” a judicial exception when the exception is “set forth” or “described” in the claim (see MPEP 2106.04(II)). Because the claims recite nature-based product limitations, the markedly different characteristics analysis is used to determine if the nature-based product limitations are a product of nature exception (see MPEP 2106.04(c)(I)). This analysis is performed by comparing the nature-based product limitations in the claims to its naturally occurring counterparts to determine if it has markedly different characteristics (see MPEP 2106.04(c)(II).
The appropriate natural counterpart to the claimed three-dimensional tissue body is aging skin as found in its natural state. The second step in the analysis requires identifying appropriate characteristics to compare. In this case, the appropriate characteristics pertain to tissue containing cells, polyelectrolytes (having polymer chains and dissociable functional groups (para 64 of the instant specification)), fragmented/defibrated collagen.
Fisher et al (Am J Pathol. 2009 Jan;174(1):101-14. Epub 2008 Dec 30.) discusses collagen fragmentation in aged human skin (title). Aged human skin is fragile because of fragmentation and loss of type I collagen fibrils, which confer strength and resiliency. We report here that dermal fibroblasts (containing DNA, which is a polyelectrolyte) express increased levels of collagen-degrading matrix metalloproteinases-1 (MMP-1) in aged (>80 years old) compared with young (21 to 30 years old) human skin in vivo. Transcription factor AP-1 and α2β1 integrin, which are key regulators of MMP-1 expression, are also elevated in fibroblasts in aged human skin in vivo. MMP-1 treatment of young skin in organ culture causes fragmentation of collagen fibrils and reduces fibroblast stretch, consistent with reduced mechanical tension, as observed in aged human skin.
Thus, the embodiments of the claims encompass naturally occurring aging skin. Thus, the claims recite a judicial exception, a natural product. [Step 2A, Prong 1: YES]
Therefore, the analysis proceeds to Step 2A Prong 2.
Step 2A (Judicial Exceptions), Prong 2: This part of the eligibility analysis evaluates whether the claims as a whole integrate the recited judicial exception into a practical application of the exception. This evaluation is performed by (a) identifying whether there are any additional elements recited in the claims beyond the judicial exception, and (b) evaluating those additional elements individually and in combination to determine whether the claims as a whole integrate the exception into a practical application. The three-dimensional tissue body is a product of nature, and no additional elements are recited in the claim that impose a practical use or application of the claimed natural products. In this regard, the claims fail to recite additional elements that integrate the judicial exception natural products into a practical application. [Step 2A, Prong 2: NO]
Step 2B (Significantly More): This part of the eligibility analysis evaluates whether the claims as a whole amount to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim (MPEP 2106.05).
Again, the claim does not recite any additional elements that add an inventive concept to the claim. As such, none of these limitations impose a practical use or application of the claimed natural products as stated in Step 2A2, and thus do not add significantly more to the exception. [Step 2B: NO]
The claims fail to recite additional elements that are sufficient to amount to significantly more than the judicial exception. Therefore, the claims do not qualify as eligible subject matter under 35 USC 101.
Second Rejection – Abstract Idea
Claim 14 is rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception (abstract idea) without significantly more. This judicial exception is not integrated into a practical application and the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below.
Step 1 (Statutory Category): This part of the eligibility analysis evaluates whether the claims fall within any statutory category. Here, the claims recite a three-dimensional tissue body comprising: cells; a fragmented extracellular matrix component; and a polyelectrolyte. This is a composition; therefore, the claims fall within a statutory category of invention. [Step 1: YES]
Step 2A (Judicial Exceptions), Prong 1: This part of the analysis evaluates whether the claim recites a judicial exception. A claim “recites” a judicial exception when the exception is “set forth” or “described” in the claim (see MPEP 2106.04(II)). The claim(s) recites at least one judicial exception. Claim 14 recites, inter alia, “wherein a thickness retention rate represented by an equation below is 80% or higher, Equation” thickness retention rate= X1/ Xo x 100 [in the equation, X1 represents a thickness of the three-dimensional tissue body after 4 days of culture, and Xo represents a thickness of the three-dimensional tissue body at the start of culture].” The claim recites at least one judicial exception. As interpreted, the claim provides a description of an abstract idea in the form of a mathematical relationship because it describes a relationship between variables or numbers. A mathematical relationship may be expressed in words or using mathematical symbols. It also recites an abstract idea (a mental process/step) because it describes mental processes include observations, evaluations, judgments, and opinions that can be performed in the human mind through division and multiplication. If a claim recites a limitation that can practically be performed in the human mind, with or without the use of a physical aid such as pen and paper, the limitation falls within the mental processes grouping, and the claim recites an abstract idea. See, e.g., Benson, 409 U.S. at 67, 65, 175 USPQ at 674-75, 674 (see MPEP 2164). The use of a physical aid (e.g., pencil and paper or a slide rule) to help perform a mental step (e.g., a mathematical calculation) does not negate the mental nature of the limitation, but simply accounts for variations in memory capacity from one person to another. It also requires making a judgment about the thickness of the tissue body based on the relationship/calculation. Thus, the claim recites at least one judicial exception, an abstract idea (mathematical relationship and mental step). [Step 2A, Prong 1: YES]. Therefore, the analysis proceeds to Step 2A, Prong 2.
Step 2A (Judicial Exceptions), Prong 2: This part of the eligibility analysis evaluates whether the claims as a whole integrate the recited judicial exception into a practical application of the exception. This evaluation is performed by (a) identifying whether there are any additional elements recited in the claims beyond the judicial exception, and (b) evaluating those additional elements individually and in combination to determine whether the claims as a whole integrate the exception into a practical application.
One consideration when determining whether a claim integrates a judicial exception into a practical application in Step 2A Prong Two is whether the additional elements amount to more than a recitation of the words "apply it" (or an equivalent) or are more than mere instructions to implement an abstract idea or other exception on a computer. As explained by the Supreme Court, in order to make a claim directed to a judicial exception patent-eligible, the additional element or combination of elements must do "‘more than simply stat[e] the [judicial exception] while adding the words ‘apply it’". Alice Corp. v. CLS Bank, 573 U.S. 208, 221, 110 USPQ2d 1976, 1982-83 (2014) (quoting Mayo Collaborative Servs. V. Prometheus Labs., Inc., 566 U.S. 66, 72, 101 USPQ2d 1961, 1965). Thus, for example, claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible. Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984 (warning against a § 101 analysis that turns on "the draftsman’s art").
Some applicable considerations to whether the limitation amounts to more than instructions to merely “apply” include (see MPEP 2106.05(f)):
Whether the claim recites only the idea of a solution or outcome i.e., the claim fails to recite details of how a solution to a problem is accomplished: The recitation of claim limitations that attempt to cover any solution to an identified problem with no restriction on how the result is accomplished and no description of the mechanism for accomplishing the result, does not integrate a judicial exception into a practical application because this type of recitation is equivalent to the words "apply it". Here, in the generic recitation of “wherein a thickness retention rate represented by equation below is 80% or higher”, the claim provides no restriction on how the result (retained thickness) is accomplished.
The particularity or generality of the application of the judicial exception: The recited tissue body and thickness retention in the claim is recited at a high level of generality as stated above and, as discussed below, well-known, routine, and conventional in the art.
Here, given that claim 14 is recited in such generic terms, it does not amount to more than a recitation of the words "apply it" (or an equivalent). [STEP 2A, Prong 2: NO]
The dependent claim 14 does not recite any additional elements that integrate the JE into practical application. Note that a judicial exception cannot form the basis for integration, so it cannot be considered to integrate the insignificant extra-solution activity into a practical application. MPEP 2106.04(d)(III) states that “Because a judicial exception alone is not eligible subject matter, if there are no additional claim elements besides the judicial exception, or if the additional claim elements merely recite another judicial exception, that is insufficient to integrate the judicial exception into a practical application.” [Step 2A, Prong 2: NO]
Step 2B (Significantly More): This part of the eligibility analysis evaluates whether the claims as a whole amount to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim (see MPEP 2106.05). This is based on an additional consideration of whether the elements in addition to the judicial exception as beyond what was well-understood, routine, and conventional to the claims. The present claim (independent claim 12) requires a three-dimensional tissue body comprising cells, fragmented extracellular matrix, and polyelectrolyte. The three-dimensional tissue body is routine, well-understood, and conventional in the art.
Matsusaki teaches a method for producing a three-dimensional tissue comprising mixing cells with a cationic substance and an extracellular matrix component to obtain a mixture, gathering the cells from the mixture to form a cell aggregate on the substrate and culturing the cells to obtain a three-dimensional cell tissue (see claim 1 of Matsusaki). The reference teaches that the cells are further mixed with a polymeric electrolyte (see claim 2 of Matsusaki). The polymeric electrolyte is selected from the group consisting of glycosaminoglycan, dextran sulfate, rhamnan sulfate, fucoidan, carrageenan, polystyrene sulfonic acid, polyacrylamide-2-methylpropanesulfonic acid, polyacrylic acid, and a combination thereof (see claim 8 of Matsusaki). The extracellular matrix component is selected from the group consisting of collagen, laminin, fibronectin, vitronectin, elastin, tenascin, entactin, fibrillin, proteoglycan, and a combination thereof (see claim 9 of Matsusaki). The concentration of the polyelectrolyte is 0.05 mg/mL or more (see claim 11 of Matsusaki). The extracellular matrix component may be used alone, or may be used in combination (para 0079). It also teaches a three-dimensional cell tissue comprising cells, an extracellular matrix component, and a polymeric electrolyte (see claims 24-25 of Matsusaki). The cells can comprise one or more types of cells selected from the group consisting of vascular endothelial cells, cancer cells, cardiomyocytes, smooth muscle cells, and epithelial cells. The concentration of the extracellular matrix component used in the present embodiment is preferably more than 0 mg/mL and less than 1.0 mg/mL (para 80).
The art demonstrates that a three-dimensional tissue body is routine and conventional in the art and, therefore, is not evidence of additional features over the judicial exception itself. [Step 2B: NO]
In view of the above, the claims are considered to be directed to the judicial exception without integration into a practical application, or adding significantly more to the claim over the judicial exception. Therefore, the claims do not qualify as eligible subject matter under 35 USC § 101.
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 (i.e., changing from AIA to pre-AIA ) 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.
Claim(s) 12 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fisher et al (Am J Pathol. 2009 Jan;174(1):101-14. Epub 2008 Dec 30.).
Fisher teaches collagen fragmentation in aged human skin (title). Aged human skin is fragile because of fragmentation and loss of type I collagen fibrils, which confer strength and resiliency. We report here that dermal fibroblasts (containing DNA, which is a polyelectrolyte) express increased levels of collagen-degrading matrix metalloproteinases-1 (MMP-1) in aged (>80 years old) compared with young (21 to 30 years old) human skin in vivo (“a three-dimensional tissue body comprising cells, a fragmented extracellular matrix component and a polyelectrolyte” as in instant claim 12). Transcription factor AP-1 and α2β1 integrin, which are key regulators of MMP-1 expression, are also elevated in fibroblasts in aged human skin in vivo. MMP-1 treatment of young skin in organ culture causes fragmentation of collagen fibrils and reduces fibroblast stretch, consistent with reduced mechanical tension, as observed in aged human skin.
Accordingly, absent evidence to the contrary, Fisher anticipates the instantly claimed invention.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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 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.
Claim(s) 1-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Matsusaki et al (US 20180355308 A1, filed 8/20/2018; published 12/13/2018) in view of Matsusaki et al (WO2018143286 A1, filed 1/31/2018; published 8/9/2018; referenced herein as “Shinji” for clarity of record).
Matsusaki teaches a method for producing a three-dimensional tissue comprising mixing cells with a cationic substance and an extracellular matrix component to obtain a mixture, gathering the cells from the mixture to form a cell aggregate on the substrate and culturing the cells to obtain a three-dimensional cell tissue (see claim 1 of Matsusaki) (“method for producing a three-dimensional tissue body, comprising: a step of obtaining a mixture by mixing a cationic substance and a . . . extracellular matrix component with cells; and a step of culturing the cells after the step of obtaining the mixture.” as in instant claim 1 in-part). The reference teaches that the cells are further mixed with a polymeric electrolyte (see claim 2 of Matsusaki) (“wherein, when obtaining the mixture, a polyelectrolyte is furthermore mixed with the cells in addition to the cationic substance and the fragmented extracellular matrix to incorporate the polyelectrolyte into the mixture” as in instant claim 5). The polymeric electrolyte is selected from the group consisting of glycosaminoglycan, dextran sulfate, rhamnan sulfate, fucoidan, carrageenan, polystyrene sulfonic acid, polyacrylamide-2-methylpropanesulfonic acid, polyacrylic acid, and a combination thereof (see claim 8 of Matsusaki) (“wherein the polyelectrolyte comprises at least one selected from the group consisting of glycosaminoglycan, dextran sulfate, rhamnan sulfate, fucoidan, carrageenan, polystyrene sulfonic acid, polyacrylamide-2-methylpropanesulfonic acid, and polyacrylic acid” as in instant claim 6 and instant claim 13). The extracellular matrix component is selected from the group consisting of collagen, laminin, fibronectin, vitronectin, elastin, tenascin, entactin, fibrillin, proteoglycan, and a combination thereof (see claim 9 of Matsusaki). The concentration of the polyelectrolyte is 0.05 mg/mL or more (see claim 11 of Matsusaki) (“wherein a concentration of the polyelectrolyte in the mixture is higher than 0 mg/mL and lower than or equal to 1.5 mg/mL” as in instant claim 7). The extracellular matrix component may be used alone, or may be used in combination (para 0079) (“wherein, when obtaining the mixture, an extracellular matrix component is furthermore mixed with the cells simultaneously or separately with respect to the cationic substance” as in instant claim 8 in-part; “the extracellular matrix component comprises at least one selected from the group consisting of collagen, laminin, fibronectin, vitronectin, elastin, tenascin, entactin, fibrillin, and proteoglycan” as in instant claim 9). It also teaches a three-dimensional cell tissue comprising cells, an extracellular matrix component, and a polymeric electrolyte (see claims 24-25 of Matsusaki) (“A three-dimensional tissue body comprising: cells; a . . . extracellular matrix component; and a polyelectrolyte.” as in instant claim 12 in-part). The cells can comprise one or more types of cells selected from the group consisting of vascular endothelial cells, cancer cells, cardiomyocytes, smooth muscle cells, and epithelial cells. (see claim 15 of Matsusaki) (“interstitial cells and endothelial cells” as in instant claim 2). The concentration of the extracellular matrix component used in the present embodiment is preferably more than 0 mg/mL and less than 1.0 mg/mL (para 80) (“wherein a total content of the extracellular matrix component . . . is 0.005 mg/mL to 1.5 mg/mL” as in instant claim 11).
The difference between Matsusaki and the instantly claimed invention is that it does not teach that the initial ECM added is a fragmented ECM (instant claim 1 in-part and 12 in-part).
Shinji teaches a three-dimensional tissue body comprising cells and collagen, and fragmented collagen (see abstract and claims of Shinji) (“a fragmented extracellular matrix component with cells” as in instant claim 1 in-part; “wherein the fragmented extracellular matrix component comprises fragmented collagen” as in instant claim 3). The reference teaches that by utilizing fragmented collagen, the cells contact and adhere to the fragmented collagen. Thereafter, the cells themselves produce proteins that constitute the extracellular matrix (ECM) (e.g., collagen such as fibrous collagen). The produced protein contacts and adheres to the fragmented collagen, thereby functioning as a cross-linking agent between the fragmented collagens, and the structuring of fibrous collagen and the like proceeds in an environment where cells exist uniformly. As a result, a three-dimensional tissue body that is more stable and in which cells are uniformly distributed is obtained.
Therefore, it would have been obvious prior to the effective filing date of the instantly claimed invention to create a three-dimensional tissue body using ECM, cells, and a cationic substance as taught by Matsusaki, where the ECM is fragmented as taught by Shinji, to arrive at the instantly claimed invention. Shinji shows that a three-dimensional tissue body can be created using fragmented collagen. One of ordinary skill would have been motivated to simply substitute one known element [first ECM of Matsusaki] for another [fragmented collagen of Shinji] to obtain the predictable result of advantageously producing a three-dimensional tissue body that has cells that are uniformly distributed as taught by the prior art.
Regarding instant claim 4, Shinji does not explicitly state that the fragmented collagen is defibrated. However, the reference teaches that the collagen is fragmented using a homogenizer such as an ultrasonic homogenizer, stirring homogenizer, or a high-pressure homogenizer. The collagen can be homogenized in an aqueous medium such as physiological saline. The examiner notes that Applicant’s instant specification describes defibration of extracellular matrix through “application of physical force with an ultrasonic homogenizer, a stirring homogenizer, a high-pressure homogenizer, and the like, for example. In a case of using a stirring homogenizer, extracellular matrix components may be homogenized as they are or may be homogenized in an aqueous medium such as physiological saline.” (see para 50 of the instant specification. Thus, absent evidence to the contrary, the fragmented collagen of Shinji is defibrated collagen as instantly claimed.
Regarding claim 10, neither reference teaches that a mass ratio of the ECM to fragmented ECM is 2:1 to 1:50. However, generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (see MPEP 2144.05(II)(A)).
Regarding claim 14, neither Shinji nor Matsusaki explicitly teach that the thickness retention rate is 80% or higher. However, Shinji does teach that there are differences in thickness of the tissue produced based on the length of time the fragmented collagen is homogenized (see example 9 of Shinji). Tissue created with collagen homogenized for 2 minutes kept its respective thickness while those homogenized for 6 minutes became thinner.
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1-9 and 11-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 6, and 12 of U.S. Patent No. US 11,179,495 B2 in view of Matsusaki et al (US20180355308 A1, 8/20/2018; published 12/13/2018).
Claim 1 of ‘495 recites “A three-dimensional tissue constructed ex vivo, comprising: cells; and
collagen, wherein the collagen includes: endogenous collagen, and a plurality of fragmented collagen pieces fragmented from each other in fragmented form derived from exogenous collagen, at least a portion of the cells is adhered to the collagen, a content of the collagen is 10 wt % to 90 wt % based on weight of the three-dimensional tissue, the plurality of fragmented collagen pieces are uniformly distributed among the cells, three-dimensionally throughout the three-dimensional tissue, the cells and the plurality of fragmented collagen pieces in the fragmented form are in contact, respectively, and an average length of the fragmented collagen pieces is from 100 nm to 200 μm”, which reads on “A three-dimensional tissue body comprising: cells; a fragmented extracellular matrix component” as in instant claim 12 in-part.
Claim 6 of ‘495 recites “A three-dimensional tissue constructed ex vivo, comprising: cells; and
collagen, wherein the collagen includes: endogenous collagen, and a plurality of fragmented collagen pieces fragmented from each other in fragmented form derived from exogenous collagen, at least a portion of the cells is adhered to the collagen, a content of the collagen is 10 wt % to 90 wt % based on weight of the three-dimensional tissue, the plurality of fragmented collagen pieces are uniformly distributed among the cells, three-dimensionally throughout the three-dimensional tissue, the cells and the plurality of fragmented collagen pieces in the fragmented form are in contact, respectively, and an average diameter of the fragmented collagen pieces is from 50 nm to 30 μm”, which reads on “A three-dimensional tissue body comprising: cells; a fragmented extracellular matrix component” as in instant claim 12 in-part.
Claim 12 of ‘495 recites “A method for producing a three-dimensional tissue, comprising:
bringing cells suspended in an aqueous medium into contact with a plurality of fragmented collagen pieces derived from exogenous collagen in the aqueous medium;” (i.e., mixing cells with fragmented extracellular matrix), “concentrating, from the aqueous medium, the cells brought into contact with the plurality of fragmented collagen pieces and the plurality of fragmented collagen pieces together; and after the concentrating, culturing the cells brought into contact with the fragmented collagen pieces, with the plurality of fragmented collagen pieces”, which reads on “A method for producing a three-dimensional tissue body, comprising: a step of obtaining a mixture by mixing . . . a fragmented extracellular matrix component with cells; and a step of culturing the cells after the step of obtaining the mixture” as in instant claim 1 in-part, “wherein the fragmented extracellular matrix component comprises fragmented collagen” as in instant claim 3 and instant claim 4.
Claim 2 of ‘495 recites “wherein the cells comprise a collagen-producing cell” and claim 5 of ‘495 recites “wherein the cells comprise one or more types of cells selected from the group consisting of vascular endothelial cells”, which reads on “wherein the cells comprise at least interstitial cells and endothelial cells.” as in instant claim 2.
‘495 does not state that the three-dimensional tissue body comprises a polyelectrolyte nor mixing a cationic substance to create the three dimensional tissue.
However, Matsusaki teaches a three dimensional tissue comprising cell, extracellular matrix component and further comprising a polymeric electrolyte (see claim 24 of Matsusaki). It also shows that a three-dimensional cell tissue can be created by a step A of mixing cells with a cationic substance and an extracellular matrix component to obtain a mixture; a step B of gathering the cells from the obtained mixture to form a cell aggregate on a substrate; and a step C of culturing the cells to obtain a three-dimensional cell tissue (see claim 1 of Matsusaki). The reference teaches that the cells are further mixed with a polymeric electrolyte (see claim 2 of Matsusaki) (“wherein, when obtaining the mixture, a polyelectrolyte is furthermore mixed with the cells in addition to the cationic substance and the fragmented extracellular matrix to incorporate the polyelectrolyte into the mixture” as in instant claim 5). The polymeric electrolyte is selected from the group consisting of glycosaminoglycan, dextran sulfate, rhamnan sulfate, fucoidan, carrageenan, polystyrene sulfonic acid, polyacrylamide-2-methylpropanesulfonic acid, polyacrylic acid, and a combination thereof (see claim 8 of Matsusaki) (“wherein the polyelectrolyte comprises at least one selected from the group consisting of glycosaminoglycan, dextran sulfate, rhamnan sulfate, fucoidan, carrageenan, polystyrene sulfonic acid, polyacrylamide-2-methylpropanesulfonic acid, and polyacrylic acid” as in instant claim 6 and instant claim 13). The extracellular matrix component is selected from the group consisting of collagen, laminin, fibronectin, vitronectin, elastin, tenascin, entactin, fibrillin, proteoglycan, and a combination thereof (see claim 9 of Matsusaki). The concentration of the polyelectrolyte is 0.05 mg/mL or more (see claim 11 of Matsusaki) (“wherein a concentration of the polyelectrolyte in the mixture is higher than 0 mg/mL and lower than or equal to 1.5 mg/mL” as in instant claim 7). The extracellular matrix component may be used alone, or may be used in combination (para 0079) (“wherein, when obtaining the mixture, an extracellular matrix component is furthermore mixed with the cells simultaneously or separately with respect to the cationic substance” as in instant claim 8; “the extracellular matrix component comprises at least one selected from the group consisting of collagen, laminin, fibronectin, vitronectin, elastin, tenascin, entactin, fibrillin, and proteoglycan” as in instant claim 9). It also teaches a three-dimensional cell tissue comprising cells, an extracellular matrix component, and a polymeric electrolyte (see claims 24-25 of Matsusaki) (“A three-dimensional tissue body comprising: cells; a . . . extracellular matrix component; and a polyelectrolyte.” as in instant claim 12 in-part). The cells can be vascular endothelial cells (see claim 15 of Matsusaki). The concentration of the extracellular matrix component used in the present embodiment is preferably more than 0 mg/mL and less than 1.0 mg/mL (para 80) (“wherein a total content of the extracellular matrix component . . . is 0.005 mg/mL to 1.5 mg/mL” as in instant claim 11). By mixing cells with a cationic substance, a polymeric electrolyte, and an extracellular matrix component, a thicker three-dimensional cell tissue can be created (i.e., retain thickness as in instant claim 14).
Therefore, it would have been obvious to modify the ‘495 claims with the cationic substance and polyelectrolyte of the Matsusaki reference to arrive at the claimed invention with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make the modification because Matsusaki teaches that having a cationic substance with the other ingredients advantageously creates thicker three-dimensional tissues.
Claims 1-3, 5-7, 9, and 11 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 8-9, 11-12, and 31 of copending Application No. 16/105625 (referenced herein as ‘625) in view of WO2018143286 A1 (referenced herein as “Shinji”).
Claim 1 of ‘625 recites “method of producing a three-dimensional cell tissue, comprising: preparing a mixture solution of a cationic substance, an extracellular matrix component, and a polymeric electrolyte; mixing cells with the mixture solution, to obtain a mixture as a liquid including the cells, the cationic substance, the extracellular matrix component, and the polymeric electrolyte; removing at least a portion of the liquid from the mixture to obtain an aggregate of the cells from the mixture; suspending the aggregate of the cells in a solution to obtain a suspension; precipitating the aggregate of the cells from the suspension to obtain cell precipitates on a substrate, the cell precipitates being stackable as a plurality of layers of cell precipitates based on repeating of the mixing, the removing, the suspending and the precipitating to construct a three- dimensional tissue; and culturing the cell precipitates to obtain the three-dimensional cell tissue.” which reads on “method for producing a three-dimensional tissue body, comprising: a step of obtaining a mixture by mixing a cationic substance and a . . . extracellular matrix component with cells; and a step of culturing the cells after the step of obtaining the mixture.” as in instant claim 1 and “when obtaining the mixture, a polyelectrolyte is furthermore mixed with the cells in addition to the cationic substance and the fragmented extracellular matrix to incorporate the polyelectrolyte into the mixture” as in instant claim 5.
Claim 8 of ‘625 recites “wherein the polymeric electrolyte includes an electrolyte selected from a group consisting of glycosaminoglycan, dextran sulfate, rharnan sulfate, fucoidan, carrageenan, polystyrene sulfonic acid, polyacrylamide-2-methylpropanesulfonic acid, polyacrylic acid, and a combination thereof” which reads on “wherein the polyelectrolyte comprises at least one selected from the group consisting of glycosaminoglycan, dextran sulfate, rhamnan sulfate, fucoidan, carrageenan, polystyrene sulfonic acid, polyacrylamide-2-methylpropanesulfonic acid, and polyacrylic acid.” as in instant claim 6.
Claim 9 of ‘625 recites “wherein the extracellular matrix component includes a component selected from a group consisting of collagen, laminin, fibronectin, vitronectin, elastin, tenascin, entactin, fibrillin, proteoglycan, and a combination thereof” and claim 31 of ‘625 recites “wherein the extracellular matrix component is Collagen I or Collagen II and the polymeric electrolyte is selected from the group consisting of glycosaminoglycan, dextran sulfate, polystyrene sulfonic acid, and a combination thereof” which reads on “wherein the extracellular matrix component comprises at least one selected from the group consisting of collagen, laminin, fibronectin, vitronectin, elastin, tenascin, entactin, fibrillin, and proteoglycan” as in instant claim 9.
Claim 11 of ‘625 recites “wherein a concentration of the polymeric electrolyte is 0.05 mg/mL or more to 0.1 mg/mL or less” which reads on “wherein a concentration of the polyelectrolyte in the mixture is higher than 0 mg/mL and lower than or equal to 1.5 mg/mL” as in instant claim 7.
Claim 12 of ‘625 recites “wherein a concentration of the extracellular matrix component is from 0.05 mg/mL or more to 0.1 mg/mL or less” which overlaps with “wherein a total content of the extracellular matrix component and the fragmented extracellular matrix component in the mixture is 0.005 mg/mL to 1.5 mg/mL” as in instant claim 11 in-part.
‘625 does not state that the ECM component is a fragmented ECM.
However, Shinji teaches a three-dimensional tissue body comprising cells and collagen, and fragmented collagen (see abstract and claims of Shinji) (“a fragmented extracellular matrix component with cells” as in instant claim 1 in-part; “wherein the fragmented extracellular matrix component comprises fragmented collagen” as in instant claim 3). The reference teaches that by utilizing fragmented collagen, the cells contact and adhere to the fragmented collagen. Thereafter, the cells themselves produce proteins that constitute the extracellular matrix (ECM) (e.g., collagen such as fibrous collagen). The produced protein contacts and adheres to the fragmented collagen, thereby functioning as a cross-linking agent between the fragmented collagens, and the structuring of fibrous collagen and the like proceeds in an environment where cells exist uniformly. As a result, a three-dimensional tissue body that is more stable and in which cells are uniformly distributed is obtained. Collagen-producing cells can be used in the tissue body (i.e., interstitial cells) (“interstitial cells” as in instant claim 2 in-part).
Therefore, it would have been obvious to modify the ‘625 claims with the fragmented ECM of the Shinji reference to arrive at the claimed invention with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make the modification because Shinji teaches that a three-dimensional tissue body that is more stable and in which cells are uniformly distributed is obtained.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
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/G.R./Examiner, Art Unit 1632
/KARA D JOHNSON/Primary Examiner, Art Unit 1632