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 .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08-25-2025 has been entered.
Applicant's amendments to the claims and arguments filed on 08-25-2025 have been received and entered. Claims 1-20 have been amended. Claims 1-20 are pending.
Priority
This application is a 371 of PCT/US2020/000004 filed on 01/15/2020 that claim priority from US provisional application 62/807,682 filed on 02/19/2019.
Claim Objections
Claim 5 and 16 are objected to because of the following informalities:
Claim 5 which depends from claim 1 recites the phrase ‘said fixing step’. However, claim 1 does not recite the term ‘fix’ or ‘fixing’ step although claim 1 recites ‘crosslinking’. It’s not necessarily clear that the words “fixing” and “crosslinking” are necessarily synonymous with one another because the specification doesn’t explicitly define them as such. In which case, one of skill in the art would not necessarily know what is refered to by the term “said fixing step” in claim 5. Thus, Claim 5 has a lack of antecedent basis for ‘said fixing step’.
Similarly, claim 16 which depends from claim 1 recites the phrase ‘said fixation solution’. Claim 1 does not recite the term ‘fixation’. Thus Claim 16 has a lack of antecedent basis for ‘said fixation solution’
Appropriate correction is required.
New-Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 6-9 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 6-9 each recite the phrase "selected from a group comprising... and...", which is open-ended Markush group language. This language makes the metes and bounds of these claims and their dependent claims vague and indefinite because it is unclear what additional, unrecited members of the Markush are encompassed by the claims. See MPEP 2173.05(h)(I):
“A Markush grouping is a closed group of alternatives, i.e., the selection is made from a group "consisting of" (rather than "comprising" or "including") the alternative members. Abbott Labs., 334 F.3d at 1280, 67 USPQ2d at 1196. If a Markush grouping requires a material selected from an open list of alternatives (e.g., selected from the group "comprising" or "consisting essentially of" the recited alternatives), the claim should generally be rejected under 35 U.S.C. 112(b) as indefinite because it is unclear what other alternatives are intended to be encompassed by the claim. See In re Kiely, 2022 USPQ2d 532 at 2* (Fed. Cir. 2022) (each independent claim recites "a selection from the group comprising a person, an animal, an animated character, a creature, an alien, a toy, a structure, a vegetable, and a fruit." … (emphasis added). "Given the breadth of variation among the specified alternatives and the use of the open-ended word ’comprising’ to define the scope of the list, we affirm the Board's conclusion that the pending claims recite improper Markush language and are indefinite under § 112(b)."). If a claim is intended to encompass combinations or mixtures of the alternatives set forth in the Markush grouping, the claim may include qualifying language preceding the recited alternatives (such as "at least one member" selected from the group), or within the list of alternatives (such as "or mixtures thereof"). Id. at 1281. See also MPEP § 2111.03.”
Note that for the purposes of examination in this action, these claims are interpreted as though each claim recites closed language for the Markush group (i.e., “selected from the group consisting of ... and....”).
Additionally, Claims 7-8 recites the phrases “other aldehydes” and “other polyhydric alcohols”, respectively. The recitation of these phrases renders the claims unclear regarding whether or not the claims are necessarily limited to the members of the Markush group. One of skill in the art would not necessarily know what is/are included or excluded for the phrases “other aldehydes” and “other polyhydric alcohols”.
Maintained-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.
Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Paniagua et al (Pub. No.: US 2014/0234434 A1, Pub. Date: Aug. 21, 2014) in view of Wiggins et al (Pub. No.: US 2002/0177116A1, Pub. Date: Nov. 28, 2002), Moore et al (WO 1996/034910 A1, 7 November 1996) and Yu et al (CN 106973888 A, Date Published: 2017-07-25).
Claims interpretation:
The specification of the claimed invention teaches that :
The penetrating agent includes molecules such as glycero1, polyethylene glycol, fatty acids, vitamins, sugars, and other molecules of similar structure (Page 3, lines 36-37). Thus, glycero1, polyethylene glycol, fatty acids, vitamins, sugars are interpreted as penetrating agent.
Counterions of both positive and negative charge are added to the pretreatment solution: such counterions include sodium ions (Na+), calcium ions (Ca++), potassium ions (K+), ferric ions (Fe+++), ferrous ions (Fe++); chloride ions (Cl-), hydroxyl ions (OH-), sulphate ions (SO4--), phosphate ions (PO4--), and other ions commonly found in human body (Page 3-4, bridging last para. in page 3 to 4). Thus, the above ions are interpreted as Counterions.
The crosslinking agent molecules include glutaraldehyde, formaldehyde, other aldehydes, and other crosslinking agents (Page 11, lines 29-30). Thus, glutaraldehyde, formaldehyde, other aldehydes, and other crosslinking agents are interpreted as crosslinking agent molecules.
The drying solution hygroscopic agent molecules include isopropyl alcohol, ethanol, propanol, acetone, other polyhydric alcohol, or other molecules currently used in the medical device industry to absorb water. Thus, the drying solution is interpreted to include isopropyl alcohol, ethanol, propanol, acetone, other polyhydric alcohol, or other molecules currently used in the medical device industry to absorb water.
Regarding claim 1-the preamble, claim 18- the preamble, claim 20- the preamble , Paniagua et al teach tissue for prosthetic implants and grafts, and methods associated therewith (title)
Regarding claim 1-step A, claim 18-step A, claim 20-step A, Paniagua et al teach pretreating the section of pericardium tissue by contacting the section of pericardium tissue with glycerol (e.g., claim 24, page 6-7). It is noted that the limitation of “counterions” in combination with penetrating agent is discussed below in the Wiggins et al reference.
Regarding claim 1-step B, claim 18-step B, claim 20-step B, Paniagua et al teaches contacting the section of pericardium tissue with one of: (i) a formalin solution; or (ii) a, glutaraldehyde solution; for a fixation period of time (e.g., claim 24, page 6-7). Also, fixation for collagen cross-linking is achieved by immersion of the tissue in 0.1-25% glutaraldehyde for between about 3 days to 5 weeks ([0056]-[0059], page 4). It is noted that the limitation of “counterions” in combination with crosslinking agent is discussed below in the Moore et al reference, and the limitation of “teach crosslinking tissue in the presence of said penetrating agent molecules, said counterions, and crosslinking agent molecules” is discussed below in the Yu reference.
Regarding claim 1-step C, claim 18-step C, claim 20-step C and D, Paniagua et al teach that contacting the section of pericardium tissue with isopropyl alcohol for a post-fixation period of time of not less than about 3 days (e.g., claim 24, page 6-7). The section of treated tissue comprises a water content of less than about 60% by weight of the section of tissue ([0032], page 2). It is noted that the limitation of “in the presence of said penetrating agent molecules and a drying agent” is discussed below in the Yu reference.
Regarding claim 1-step D, claim 19- the step of removing water, claim 20-step E, Paniagua et al teaches (i) drying the section of pericardium tissue (e.g., claim 24) and drying the section of pericardium tissue further comprises placing the section of pericardium tissue between two acrylic plates (e.g., claim 38).
Regarding claim 1-step D- the wherein clause, claim 19-the step of forming a dry tissue, claim 20-step E, it is noted that the claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. Examples of claim language, although not exhaustive, that may raise a question as to the limiting effect of the language in a claim are “adapted to” or “adapted for” clauses, “wherein” clauses, and “whereby” clauses.
The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a “whereby” clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention.” Id. However, the court noted (quoting Minton v. Nat ’l Ass ’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Id. See MPEP § 2111.04.
For the sake of compact prosecution, claim 1-step D- the wherein clause, claim 19-the step of forming a dry tissue component, claim 20-step E, are interpreted as that the dried tissue component can resist cracking due to bending. Paniagua et al teaches treating the tissue for preventing calcification ([0053], page 4). Also, Paniagua et al teaches in [0069] that (i) the treatment steps provided an ultimate tensile strength of greater than 25 MegaPascals; (ii) The combination of tissue pliability and tensile strength is sought for purposes of producing a material having property characteristics suitable for being physically manipulated to form prosthetic implants; (iii) The preparation and fixation techniques produce tissue membrane material that may be rendered and used at lesser thicknesses than typically rendered in the prior art. Thinner membranes are more pliable (see [0069], page 5).
Although ions such as sodium ions (Na+), calcium ions (Ca++), potassium ions (K+), ferric ions (Fe+++), ferrous ions (Fe++); chloride ions (Cl-), hydroxyl ions (OH-) inherently exist in animal tissue/fluid, Paniagua et al doesn’t teach the use of solution of counterions during pretreating and crosslinking steps. However, Wiggins et al and Moore et al cure the deficiency.
Regarding claim 1-step A, claim 18-step A, claim 20-step A, Wiggins et al teaches preserving living biological materials that enable organs, tissues and cells to be stored for extended periods (Abstract). Preserving the viability of living biological materials, comprising either TMAO or PEG 1500 (polyethylene glycol), in combination with sodium chloride and calcium chloride ([0016], page 2). Preservation solutions of the present invention may also include one or more ions such as in solution of calcium sulfate or calcium chloride ([0013], page 2).
Regarding claim 1-step B, claim 18-step B, claim 20-step B, Moore et al teaches a method for improving crosslinking in a tissue sample, using sodium chloride salt through maintaining ionic interactions : method for cross-linking a proteinaceous tissue sample, the improvement comprising maintaining the ionic interaction between the protein molecules comprising the sample by immersing the sample in an aqueous solution of a salt, and the salt being selected form the group of salts which are capable of penetrating the sample (e.g., claim 1, page 13), and wherein said salt is either sodium chloride (e.g., claim 2, page 13).
Paniagua et al , Wiggins et al, and Moore et al do not specifically teach crosslinking tissue in the presence of said penetrating agent molecules, said counterions, and crosslinking agent molecules, and drying tissue in the presence of said penetrating agent molecules and a drying agent. However, Yu et al cure the deficiency.
Regarding claim 1-step B, claim 18-step B, claim 20-step C, and Regarding claim 1-step C, claim 18-step C, claim 20-step D and E, Yu et al teaches a storing liquid of a pathological tissue specimen (Abstract) and Embodiment 1: A pathological tissue specimen preservation liquid, which is prepared by mixing following raw materials according to parts by weight: 2 g of potassium sorbate, 10 g of industrial ethanol, 1g of glycerol, 2g of glutaraldehyde, 8.5g of sodium chloride, nano-silver is 0.6 g, citric acid 10g, water 60g (Page 4, Embodiment 1). Yu et al also stated that one also can make several simple deductions or replacements, and all of which should be considered to belong to the protection scope of the present invention (Page 4, first Para). Since a tissue specimen preservation liquid can be prepared with the presence of ethanol, glycerol (penetrating agent), glutaraldehyde (crosslinking agent), sodium chloride (counterions) simultaneously, one of ordinary skill in the art would be motivated to place tissue component pretreated with penetrating agent and counterions directly into fixation solution or drying solution without intermediate step such as rinsing the tissue component, with a reasonable expectation of success.
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the rejected claims to combine the teachings of prior art to modify the method of Paniagua et al to by using counterions as taught by Wiggins et al and Moore et al and using a storing liquid of a tissue prepared by mixing glycerol, glutaraldehyde, and sodium chloride together in 1 solution as taught by Yu et al as instantly claimed, with a reasonable expectation of success. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to do so because Wiggins et al provide explicit advantage of preserving the viability of living biological materials, comprising either TMAO or PEG 1500, in combination with sodium chloride and calcium chloride ([0016], page 2). Moore et al provide explicit advantage of method for improving crosslinking in a tissue sample, using sodium chloride salt through maintaining ionic interactions (e.g., claim 1, page 13). Yu et al provide explicit advantage of preservative liquid which is colorless and transparent liquid, no pungent smell, sterilizing and anti-mildew performance is excellent (Page 3). Thus, the arts teach the cross-linking tissue sample can be improved with the presence of salt such as sodium chloride, and the penetrating agent, counterions, crosslinking agent, drying solution can be prepared in different or the same solution for preparation of a tissue component. One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Paniagua et al, Wiggins et al, Moore et al and Yu et al were all successful in preserving biological tissue and provide detailed instruction with step of preparation of the tissue.
Regarding claim 2, 3, and 4, as mentioned above, Yu et al teaches a storing liquid of a pathological tissue specimen by mixing all together of industrial ethanol, glycerol, glutaraldehyde, sodium chloride (Page 4, Embodiment 1). Additionally, it is noted that ethanol, glycerol, glutaraldehyde, and sodium chloride are structurally and functionally similar to drying agent, penetrating agent, crosslinking agent, counterions claimed in the instant application. Thus, it is obvious that they should function as required by the claim: to prevent the diffusion of penetrating agent that are integrated into the structure, during tissue preparation, using routine experimentation. It is noted that: Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430,433 (CCPA 1977).
Regarding claim 5, as mentioned above, Yu et al teaches a storing liquid of a pathological tissue specimen that can be used to preserve tissue and prepared by mixing together glycerol, glutaraldehyde, and sodium chloride. Thus, it would be obvious for one of ordinary skill in the art to use the liquid directly on tissue specimen without rinsing to remove pretreatment solution containing penetrating agent and counterions such as glycerol and sodium chloride.
Regarding claim 6, 7, 8, Paniagua et al teaches pretreating the section of tissue with glycerol before contacting the section of tissue with one or more of isopropyl alcohol, glutaraldehyde and formalin ([0021], page 2).
Regarding claim 9, Wiggins et al teaches preserving the viability of living biological materials, comprising either TMAO or PEG 1500, in combination with sodium chloride and calcium chloride ([0016], page 2) and Preservation solutions may also include one or more ions such as in solution of sodium sulfate and calcium chloride ([0013], page 2).
Regarding claim 10, Paniagua et al further teaches immersion of the tissue in 100% glycerol (13.69 M, in pretreatment step) for up to 6 weeks at between 4 to 37° C ([0058], page 4).
Regarding claim 11-12, Yu et al teaches a preservation liquid (being used in crosslinking and drying step) prepared by mixing 2 g of potassium sorbate, 10 g of industrial ethanol, 1g of glycerol, 2g of glutaraldehyde, 8.5g of sodium chloride, nano-silver is 0.6 g, citric acid 10g, water 60g (Page 4, Embodiment 1). Yu et al also stated that one also can make several simple deductions or replacements, and all of which should be considered to belong to the protection scope of the present invention (Page 4, first Para). Therefore, it would have been obvious to one of ordinary skill in the art, to have used the teachings of Yu et al to optimize the method to have a required amount of penetrating agent in fixation solution or the drying solution, to achieve a desired tissue flexibility, using routine experimentation, with a reasonable expectation of success.
Regarding claim 13, 14, 15, Wiggins et al teach the use of sodium salt with penetrating agent and the sodium chloride at a concentration of more than about 30 mM ([0016], Page 2), and Moore et al teaches that adding sodium salt improves crosslinking (e.g., claim 1, page 13) with the use of about 2.0 (2000mM) to about 5.0 M (5000mM) NaCl in the medium (see page 4, 3rd para), and Yu et al teaches preparation of a preservation liquid mixing 2 g of potassium sorbate, 10 g of industrial ethanol, 1g of glycerol, 2g of glutaraldehyde, 8.5g of sodium chloride, nano-silver is 0.6 g, citric acid 10g, water 60g (Page 4, Embodiment 1). As mentioned above, Yu also stated one also can make several simple deductions or replacements, and all of which should be considered to belong to the protection scope of the present invention (Page 4, first Para). Therefore, taken together, it would have been obvious to one of ordinary skill in the art, to use the teachings of Wiggin et al, Moore et al and Yu et al and optimize the methods to have an amount of counterions (at least three hundred millimolar) to achieve a desired amount of counterions within pretreating step, crosslinking step or drying step, using routine experimentation, with a reasonable expectation of success.
Regarding claim 16, Paniagua et al teaches immersion of the tissue in 0.1-25% glutaraldehyde for between about 3 days to 5 weeks ([0059], page 4).
Regarding claim 17, Since Paniagua et al teaches immersion of the tissue in 100% glycerol for up to 6 weeks at between 4 to 37° C ([0058], page 4). Thus, One of ordinary skill in the art would be able to optimize pretreating step with penetrating agent such as glycerol for time period up to 6 weeks such as five minutes to twenty-four hours using routine experimentation with a reasonable expectation of success. Additionally, Paniagua et al teaches fixation of tissue component: immersion of the tissue in 0.1-25% glutaraldehyde for between about 3 days to 5 weeks ([0059], page 4).
Response to Arguments
Applicant's arguments filed 08-25-2025 have been fully considered but they are not persuasive.
1. Applicant argues that Examiner is using improper hindsight and is simply choosing certain steps/solutions from the aforementioned cited prior arts to construct the methods/solutions presently claimed (Remarks, Page 8).
Response to Arguments: in response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the instant case, the Examiner has only relied upon what was known in the art via the teachings of the cited references (Paniagua et al; Wiggins et al; and Yu et al).
2. Applicant argues that Applicant respectfully submits that one of ordinary skill in the art, without the benefit of the present invention, would have had no motivation to combine the cited prior art references (Remarks, Page 9).
Response to Arguments:
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, . One of ordinary skill in the art would have been motivated to do so because Wiggins et al provide explicit advantage of preserving the viability of living biological materials, comprising either TMAO or PEG 1500, in combination with sodium chloride and calcium chloride ([0016], page 2). Moore et al provide explicit advantage of method for improving crosslinking in a tissue sample, using sodium chloride salt through maintaining ionic interactions (e.g., claim 1, page 13). Yu et al provide explicit advantage of preservative liquid which is colourless and transparent liquid, no pungent smell, sterilizing and anti-mildew performance is excellent (Page 3). Thus, the arts teach the cross-linking tissue sample can be improved with the presence of salt such as sodium chloride, and the penetrating agent, counterions, crosslinking agent, drying solution can be prepared in different or the same solution for preparation of a tissue component. One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Paniagua et al, Wiggins et al, Moore et al and Yu et al were all successful in preserving biological tissue and provide detailed instruction with step of preparation of the tissue.
3. Applicant argues that Wiggins prior art teaches away from the use of penetrating molecules as taught by the Paniagua prior art. Wiggins instead selects non-penetrating solutes, such as Class I disaccharides and trisaccharides (e.g., raffinose, trehalose, sucrose) that are too large to cross membranes, and Class II solutes (e.g., TMAO, betaine, taurine, certain sugars) that generally do not passively cross membranes and are only taken up under osmotic stress (see paragraphs [0068]-[0069]). The Wiggins prior art further states that its preservative solutions function by isolating cells from external stimulatory signals and "preventing the opening of ion channels, thereby maintaining the cells in a state of dormancy."(paragraph [0081]), i.e., preventing active transport. Furthermore, the Wiggins prior art emphasizes that "the absence of conventional cryoprotectants [such as glycerol] at concentrations greater than 5% is preferred" due to their toxicity (paragraph [0080]) ….. Wiggins expressly excludes penetrating molecules, relying instead on non-penetrating solutes to maintain dormancy by preventing ion channel opening (paragraph [0081 ]) (Remarks, page 9-10).
Response to Arguments:
Applicants have engaged in selective reading of the teachings of Wiggins et al to formulate the grounds for teaching away. It should be noted that the instant specification of the claimed invention teaches that the penetrating agent includes molecules such as glycero1, polyethylene glycol, fatty acids, vitamins, sugars, and other molecules of similar structure (Page 3, lines 36-37). Additionally, Wiggins et al teach when employing freezing techniques to preserve biological materials, high concentrations (approximately 10% by volume) of cryoprotectants, Such as glycerol, dimethylsulfoxide (DMSO), glycols or propanediol, are often introduced to the material prior to freezing in order to limit the amount of damage caused to cells by the formation of ice crystals during freezing ([0007] page 1). Thus, Wiggins et al provide teachings that satisfy the claim requirements. Even with Applicant’s attempt to use selective reading of certain Solutes to formulate the grounds for teaching away, it is noted that the Wiggins et al teach the use of both Class I Solutes and Class II Solutes and Class II Solutes such as glucose can be actively taken up with the help an osmotic insult ([0069]) which still satisfy the claim limitations. The claims recite the term “comprising” which is which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004) (seeMPEP 2111.03 (I)). There is no requirement to not using other mean to improve the penetration of the agent.
Applicants have further engaged in selective reading of the teachings of Wiggins et al and cite [0080] to emphasizes the absence of conventional cryoprotectants. It is noted that paragraph [0080] emphasizes the high concentrations greater than 5% of cryoprotectants and do not prevent the use of these, and paragraph [0080] further teaches that these compounds probably protect from freezing damage by inducing amorphous. Additionally, Wiggins et al specifically teach “the present invention provides solutions for preserving the viability of living biological materials, comprising either TMAO or PEG 1500 (polyethylene glycol), in combination with sodium chloride and calcium chloride …...” ([0016], page 2).
Wiggins et al do not exclude penetrating molecules in paragraph [0081] and there is no teaching “non-penetrating solutes to maintain dormancy” as applicant asserted in paragraph [0081]. In fact, Wiggins et al specifically teach the use of penetrating molecules “trimethyl amine oxide (TMAO) or PEG 1500 (polyethylene glycol), in combination with sodium chloride and calcium chloride” ([0016], page 2).
4. Applicant argues that the Moore reference teaches the use of very high osmolarity solutions, stating that "The osmolality (represented by the Greek letter µ) of the storage medium of the present invention is higher than the osmolality of 3.0 M NaCl solution, e.g., 4500 mOsm, and in a particularly advantageous embodiment, the osmolality is higher than about 6000 mOsm." (page 3, lines 27-30). In contrast, while the Paniagua prior art discloses several methods and solutions for crosslinking tissue (paragraphs [0056]-[0061 ]), none of these teach the use of such high salt concentrations. At most, the Paniagua prior art discloses additives in the range of about 100-1000 mM, with a preferred value of approximately 684 mM (paragraph [0061 ]), which is substantially lower than Moore's teachings.
Furthermore, Applicant asserts that Moore teaches the sugar as the counterion and the salt as the penetrating molecule, rather than as a counterion, as in the present invention. Moore explains that as the salt penetrates the tissue, it disrupts ionic interactions in collagen fibrils, while the high sugar concentration maintains osmolarity and induces short-term fibril aggregation (page 3, lines 18-26). Thus, Moore teaches away from using salt as a counterion, as taught by the present invention (Remarks, page 10-11).
Response to Arguments:
Applicants again have engaged in selective reading of the teachings of Moore et al to formulate the grounds for teaching away. The claims do not recite any concentration and Paniagua et al do not prevent the use of high salt concentrations. It is noted that Paniagua et al discloses additives in the range of about 100-1000 mM paragraph ([0061], page 4), and Moore et al also teach the use of “a number of commonly used buffers such as phosphate buffered saline (PBS). Other suitable buffers include those containing potassium or sodium phosphate, or potassium or sodium chloride …... preferably at concentrations of from about 0.2 to about 1.0 M” (see page 7). Thus, it is indicating that additive/salt concentrations were recognized in the prior art to be a result-effective variable. A person of ordinary skill in the art would have been motivated to perform the optimization for salt concentration for tissue preservation.
Applicant voice an opinion to formulate the grounds for teaching away that Moore et al teach the sugar as the counterion and the salt as the penetrating molecule which is not persuasive. There is not deniable that Moore et al used both salt and sugar which satisfy the requirements of the claims. According to MPEP 716.01(c) (II): arguments by applicant cannot take the place of evidence: Arguments presented by the applicant cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965) and In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). Examples of statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor.
5. Applicant argues that the Paniagua prior art teaches of prosthetic implants, grafts, and related methods, whereas the Yu prior art teaches a solution for preserving pathological tissue specimens. In the art, a "pathological tissue specimen" is understood to refer to tissue intended for microscopic evaluation to diagnose or manage a medical condition, not for implantation. Thus, Yu expressly teaches away from maintaining the biomechanical integrity required for implantable tissues (Remarks, page 11).
Response to Arguments:
Applicant’s arguments regarding an intended use for the product produced by the claimed methods are not persuasive because both Paniagua et al and Yu et al teach tissue preservation for medical use. Even if the intended use is recited in the claim, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Furthermore, Paniagua et al stated that “a method of preparing a tissue for medical use” ([0021], page 2). Thus, Paniagua et al teach preparing a tissue for medical use such as medical research including preserving pathological tissue specimens for medical research. Thus, Applicant’s arguments are not persuasive.
Conclusion
No claim is allowed.
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/KHOA NHAT TRAN/Examiner, Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632