DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claims 1-20 are pending, all of which have been considered on the merits.
Priority
Acknowledgement is made of Applicants claim for benefit under 35 USC 120 as a continuation of prior-filed application 16/513183 (filed 7/16/2019, now abandoned), which claims benefit under 35 USC 120 as a continuation of prior-filed application 14/255,559 (filed 4/17/2014, now abandoned), which claims benefit under 35 USC 120 as a continuation of prior-filed application 12/348188 (filed 1/2/2009, now USP 8735054), which claims benefit under 35 USC 119(e) to US provisional application 61/019169 (filed 01/04/2008).
Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 or 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)
Regarding claims 1-5 and 7-20: The subject matter of claims 1-5 and 7-20 are supported in the prior-filed applications, and thus claims 1-5 and 7-20 have an effective filing date of 1/4/2008.
Regarding claim 6: None of prior-filed applications 14/255559, 12/348188 or 61/019169 provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for claim 6 of this application. Instant claim 6 permits for a range of up to about 150 MM (mega moles) of salt. The prior-filed applications do not contemplate this high of a concentration. The first disclosure of the subject matter of current claim 6 was in prior-filed application 16/513183 (filed 7/16/2019; see original claim 6). Thus the effective filing date of claim 6 is considered to be the filing date of the 16/513183 application, and thus claim 6 has an effective filing date of 11/3/2023.
Claim Interpretation
For clarity, the following notes are made on claim interpretation:
The claims are drawn to a composition comprising (a) an acellular tissue matrix, and (b) a solution.
The specification (at ¶0075) defines the (a) ‘acellular tissue matrix (ATM)’ as ‘a tissue-derived structure that is made from any of a wide range of collagen-containing tissues by removing all, or substantially all, viable cells and all detectable subcellular components and/or debris generated by killing or lysing cells’. This definition excludes tissues which have been subject to cellular disruption, but from which the cells and/or cell debris has not been removed.
Various claims define ranges as “about X” (emphasis added). There is no explicit definition for the term “about” in the instant specification, so the term is being given its broadest reasonable interpretation as encompassing values slightly above and below the recited values.
In claim 6 the measure of unit “MM” is given its standard meaning in the art of ‘mega moles’, thus claim 6 permits for the salt concentration to be up to about 150000 M.
Claim 7 further defines the at least one polyhydroxy compound of the solution of claim 1. Claims 7-19 are read in light of claim 1, meaning each of the recited species are limited to polyhydroxy compounds of the recited species (e.g.in claim 7 it is stated the polyhydroxy compound can be a surfactant, this is interpreted as limiting to surfactants that are polyhydroxy compounds).
Specification
The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). Correction of the following is required:
Claim 6 states the salt concentration is up to about 150 MM in the solution. The specification does not provide antecedent basis for this range. The highest salt concentration disclosed by the specification is 2 M (See, e.g. ¶0006, 0017). The specification does provide support for salt concentrations up to about 150 mM (See ¶0023).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 9 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
In claim 9 the species “TWEEN 20” and “TWEEN 80” render the claim indefinite because “TWEEN” is a trademark. The use of a trademark or trade name in a claim as a limitation to identify or describe a particular material or product renders the claim indefinite. Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). A trademark or trade name does not properly identify any particular material or product, but rather the source or origin of a product; thus the claim scope is uncertain since the trademark fails to define the actual material or product. Use of a trademark or trade name in a claim to identify or describe a material or product not only renders the claim indefinite, but is also an improper use of the trademark or trade name.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 9, 11 and 13 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Regarding claim 9: The species of cetyl alcohol, oleyl alcohol, cocamide MEA, cocamide DEA and cocamide TEA are not polyhydroxy compounds, and thus do not further limit (or properly correspond with) parent claims 7 and 1.
Regarding claim 11: The species of DMPS is not a polyhydroxy compound, and thus does not further limit (or properly correspond with) parent claims 7 and 1.
Regarding claim 13: The species of dimethyl sulfoxide is not a polyhydroxy compound, thus it do not further limit (or properly correspond with) parent claims 7 and 1.
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
The following is a quotation of the appropriate paragraphs of pre-AIA 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 –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 1, 4-7, 14, 15, and 18-20 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Goldstein et al (WO 04/052098).
Goldstein et al disclose a cryopreservation solution, and a method of sterilizing and cryopreserving animal tissue for storage.
The method of Goldstein et al involves placing a tissue into a package, adding the cryopreservation solution to the tissue in the package, freezing the package, irradiating the package for terminal sterilization and transferring the package to extended storage. For subsequent use, the package is removed from storage, the tissue is thawed and then implanted into an animal (See ¶0031). The tissue to be treated may be human or non-human, and preferably are collagen-rich tissues (See ¶0033). The tissue may be decellularized prior to preservation or they may be non-decellularized (i.e. living) tissues (See ¶0035).
The cryopreservation solution generally contains (a) a biocompatible buffer, (b) a cell-impermeant constituent, (c) a cell-permeant constituent, and (d) a radical scavenger (See ¶0015). More specifically, the (a) biocompatible buffer may be PBS, HEPES, MOPS, TRIS, saline buffers such as borate, bicarbonate, carbonate, cacodylate, or citrate ions, and mixtures thereof. The buffer is to maintain the solution’s pH from 6 to 8, preferably 7.4 (See ¶0037-0040, particularly 0038). Sodium chloride (NaCl) may be part of the buffer system. NaCl may be present at 0.02 to 0.5 M, more preferably about 0.07 to about 0.3 M, and most preferably about 0.154 M NaCl (See ¶0040). The (b) cell-impermeable constituent may be proteins, serums, monosaccharides including sucrose, trehalose, polysaccharides including dextran, agarose and alginate, long chain polymers including PVP, hydroxyethyl starch, derivatives and mixtures thereof (See ¶0041-0044, particularly 0043). The (c) cell permeable constituent may be an alcohol, such as propanediol, isopropanol, ethanol, t-butanol, mannitol and glycerol; glycols, such as ethylene glycol and propylene glycol; trimethylamine; acetate; aldoses; ketones, xylose; erythrose; arabinose; ribose; flucose; fructose; galactose; and mixtures thereof (See ¶0045-0049, particularly 0048). The cell permeant constituent may be present in an amount of from 5 to 30%, more preferably 10-20%, most preferably 15% of the solution (See ¶0049). Finally, the radical scavenging compound may be various acids and salts that ionize in water, such as sodium ascorbate, carotenoids, 1-ascorbic acid, d-isoascrobic acid, sodium sulfite, sodium metabisulfite, sulfur dioxide, sodium nitrate, and others (See ¶0050-0055, particularly 0053).
In Example 2, Goldstein et al teach placing decellularized pulmonary valve leaflets in a cryopreservation solution comprising PBS (containing 0.154 M NaCl), PVP (12.5% (w/v)), isopropanol (15% (v/v)), and sodium ascorbate (0.5 M).
The composition created in Example 2 (prior to freezing) reads on the instant claims as follows:
Regarding claim 1: The decellularized pulmonary valve reads on an acellular tissue matrix. The cryopreservation solution reads on a solution. The PBS buffer reads on a biocompatible buffer. PBS contains 0.154 M NaCl, which reads on a salt. The sodium ascorbate reads on at least one polyhydroxy compound.
Though not specifically disclosed in the Example, Goldstein et al teach phosphate buffers in their compositions buffer to pH of 7-8, which reads on a pH ranging from about 4.0 to about 7.5 (noting that even a pH of 8 reads on about 7.5, thus 7-8 is fully within the claimed range), and more preferably a pH of 7.4 (See ¶0038), which is squarely within the claimed range.
Regarding claim 4: PBS is a phosphate buffer.
Regarding claim 5: PBS buffer contains the salt NaCl.
Regarding claim 6: The NaCl is present in the PBS buffer at a concentration of 0.154 M, which is within the range of up to about 150 MM.
Regarding claim 7: The sodium ascorbate satisfies the limitation of a polyhydroxy compound, and further reads on a tissue stabilizer as well as a biocompatible co-solute.
Regarding claims 14 and 15: Following the discussion of claim 7, the sodium ascorbate satisfies the limitation of a polyhydroxy compound, and more specifically a tissue stabilizer, and is present at 0.5 M (which satisfies the limitation of 500 mM or less), which is 9.9% w/v (which satisfies the limitation of about 10% (w/v) or less).
Regarding claims 18 and 19: Following the discussion of claim 7, the sodium ascorbate satisfies the limitation of a polyhydroxy compound, and more specifically a biocompatible solute, and is present at 0.5 M (which satisfies the limitation of 1 M or less), which is 9.9% w/v (which satisfies the limitation of about 20% (w/v) or less).
Regarding claim 20: The pH range of 7-8, and preferably 7.4 (achieved by use of PBS buffer) is considered to read on about 6.0, and thus the solution is considered to satisfy the limitation of having a pH ranging from about 5.4 to about 6.0.
Claim 6 is rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Sun et al (US Patent 8735054).
In Example 1, Sun et al disclose an acellular tissue matrix (ATM) preserved in an aqueous preservation solution. The aqueous preservation solution comprises a biocompatible buffer, with 20 mM citrate buffer pH 5.4 and 4 mM citrate and 25 mM phosphate buffer, pH 6.4 being preferred; ATM stabilizers, with trehalose being preferred; and added NaCl (See col. 27, ln 65-col. 54).
The ATM in the preferred aqueous preservation solution satisfies the claim limitations as follows:
Regarding claim 6: The ATM reads on an acellular tissue matrix. The aqueous preservation solution reads on the solution, as it comprises a biocompatible buffer, NaCl, which reads on a salt, and trehalose, which reads on at least one polyhydroxy compound. The solution has a pH of 6.4, which is squarely within the claimed range.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claims 1-7, 13-20 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Goldstein et al (WO 04/52098).
The teachings of Goldstein et al are set forth above. The specific composition disclosed in Example 2 anticipates several claims as described above, but Goldstein et al further teach variations on the cryopreservation solutions which reads on additional claims as follows:
Regarding claims 1-4: The decellularized tissue matrix clearly reads on an acellular tissue matrix as claimed. The cryopreservation solution is compared to the solution as claimed:
The (a) biocompatible buffer reads on a biocompatible buffer. Goldstein et al teach suitable biocompatible buffers include one or more of, inter alia, PBS (a phosphate buffer), a citrate ion buffer (a citrate buffer). Thus Goldstein et al is found to render obvious use of a phosphate buffer, a citrate buffer and/or combinations of a phosphate and citrate buffer. This conclusion of obviousness is based on a teaching in the reference that the different disclosed buffers can be substituted for one another. Substitution of one element for another known in the field, wherein the result of the substitution would have been predictable, is considered to be obvious. See KSR International Co. v Teleflex Inc 82 USPQ2d 1385 (US 2007) at page 1395. One would have had a reasonable expectation of successfully using a phosphate buffer, a citrate buffer or a combination of a phosphate and a citrate buffer based on the disclosure of Goldstein et al and the ability of the ordinary artisan to optimize within the general teachings of the art.
The biocompatible buffer is taught to buffer the solution to a pH ranging from 6 to 8 (which falls within the claimed range of about 4.0 to about 7.5), and specifically 7.4 (which falls squarely within the claimed range of about 4.0 to about 7.5).
Regarding claims 5-6: Goldstein teach the buffer can contain the salt NaCl at a concentration of 0.02 to 0.5M, preferably 0.07 to about 0.3 and most preferably 0.154 M NaCl. 0.154 is within the range of up to about 150 MM.
Regarding claims 7, 13, 16, and 17: The (b) cell-impermeable constituent may be sucrose, trehalose, dextran, agarose, alginate, and/or hydroxethyl starch, each of which read on at least one polyhydroxy compound, and which further satisfy the limitation of a tissue stabilizer as well as a biocompatible solute.
The (c) cell permeable constituent may be propandiol, mannitol, glycerol, ethylene glycol, propylene glycol, xylose, erythrose, arabinose, ribose, glucose, fructose, and/or galactose, each of which also read on at least one polyhydroxy compound, and which further satisfy the limitation of a tissue stabilizer as well as a biocompatible solute.
Goldstein et al is found to render obvious use of any of sucrose, trehalose, dextran, agarose, alginate and/or hydroxyethyl starch as the (b) cell-impermeable constitute, and use of any of propandiol, mannitol, glycerol, ethylene glycol, propylene glycol, xylose, erythrose, arabinose, ribose, glucose, fructose and/or galactose as the (c) cell permeable constituent. This conclusion of obviousness is based on a teaching in the reference. One would have had a reasonable expectation of successfully using any of the options disclosed by Goldstein based on the disclosure of Goldstein et al that all agents are suitable as cell-impermeable constituents for use in the cryopreservation solution.
The ethylene glycol and propylene glycol satisfy the limitation of tissue stabilizer (claim 13).
The ethylene glycol and propylene glycol satisfy the limitation of biocompatible solutes, and specifically sugar alcohols (claim 16).
The sucrose, trehalose, mannitol, xylose, erythrose, arabinose, ribose, glucose, fructose, and galactose each satisfy the limitation of biocompatible solutes, and specifically sugars (claims 16-17).
Regarding claims 14, 15, 18 and 19: Goldstein et al teach any of the cell-impermeable constituents (including sucrose, trehalose, dextran, agarose, alginate, and/or hydroxethyl starch, each of which read on at least one polyhydroxy compound, and which further satisfy the limitation of a tissue stabilizer as well as a biocompatible solute) can be present at a concentration of 5-30% and more preferably 10-14%. Goldstein et al teach any of the cell permeable constituents (including propandiol, mannitol, glycerol, ethylene glycol, propylene glycol, xylose, erythrose, arabinose, ribose, glucose, fructose and/or galactose) can be present in solution at a concentration of 5-30%, and more preferably 10-20% (v/v) and most preferably about 15% (v/v).
Goldstein et al does not disclose the concentrations in w/v% or M, so exact comparison cannot be made. However it is submitted that generally, differences in concentration are considered prima facie obvious absent evidence of criticality. Goldstein et al disclose the general conditions of the instant claims, it would have been well within the skill level of the artisan of ordinary skill to experiment within the general conditions of Goldstein et al to arrive at workable concentrations for each specific component. See MPEP 2144.05 (II).
Regarding claim 20: The pH range of 6-8 overlaps with the claimed range of 5.4 to about 6.0. A prima facie case of obviousness exists where the claimed ranges overlap or lie inside the ranges disclosed by the prior art, or are at least close. See MPEP 2144.05(I).
Claims 1-7 and 13-20 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Sun et al (US 2006/0073592), evidenced by Millipore-Sigma “1X Phosphate-buffered saline (PBS) Recipe Calculator” (2022), B. Braun Medical, Inc “Lactated Ringers” (2020), and Millipore Sigma “Buffer Reference Center” (2022).
Sun et al disclose methods of storing acellular tissue matrices (ATM) in which a substantial portion of water in the matrices is ‘replaced’* with water-replacing agents (WRA), as well as compositions made by these methods (“water-replaced ATM”) (See abstract).
The ATM is defined as a tissue-derived structure that is made from any of a wide range of collagen-containing tissues by removing all, or substantially all, viable cells and all detectable subcellular components and/or debris generated by killing cells (See ¶0032). The definition of ATM is the same as that in the current application, thus the ATM of Sun et al is the same as that required in the instant claims. Sun et al teach the ATM can be derived from dermis, pericardium, cardiac valves, ligaments, tendons, vascular tissues, and more (See ¶0036).
The WRA may be any chemical compound that ‘substitutes’ for water and (a) provides a similar hydrogen bonding for structural and consequent functional preservation of the ATM, but (b) lacks, or substantially lacks, the properties of water that result in subsequent damage to the ATM. The WRA may be, inter alia, polyhydroxy compounds such as glycerol (See ¶0060-0061, ¶0070). The WRA is used diluted in an aqueous solvent such as water, normal saline, PBS, Ringer’s lactate, or a standard tissue culture medium (See ¶0062). The solution comprising the WRA may further contain supplementary agents that serve to prevent or minimize the damage that can occur to ATM, such as, inter alia, sugar alcohols such as mannitol and sorbitol (See ¶0063). The solutions comprising the one or more WRA are comparable to the (b) solution of the instant claims.
Sun et al teach the process of generating the ‘water-replaced ATM’ involves exposing a fully hydrated or partially hydrated ATM to increasing concentrations of a solution comprising one or more WRA (See ¶0067). Sun et al teach variables such as the starting/intermediate/final concentration of the WRA in the solution, the rate of increase, the temperature, the duration of contact between the ATM and the solution containing WRA, will all vary depending on the specific ATM (tissue type, density, volume, etc). Generally, incubations of the ATM in the solution containing WRA will be under conditions effective to achieve equilibrium. Sun et al teaches modification and optimization of variables related to the processing of the ATM to generate the ‘water-replaced ATM’ would have been within the purview of the artisan of ordinary skill (See ¶0069).
Sun et al exemplify generation of acellular human skin (acellular dermal matrix (ADM)). The ADM is a species of ATM (See Example 1 ¶0090-0096). Sun et al perform ‘water replacement’ on the ADM by incubating the ADM in three solutions comprising glycerol (as WRA) in normal saline (aqueous solvent), wherein the glycerol concentration is increased in each subsequent incubation step, up to final concentration of 85% (v/v) glycerol. The glycerolized ADM at the end of the final incubation step contained about 60% (w/w) (in a thicker ADM sample) or about 70% (w/w) (in a thinner ADM sample) (See ¶0098-0100).
The composition comprising the glycerolized ADM samples within the final 85% (v/v) glycerol/normal saline solution is relied upon for this rejection:
Regarding claims 1 and 20: The ADM reads on the (a) ATM of the instant claim. The solution comprising 85% (v/v) glycerol in normal saline is comparable to the (b) solution of the instant claim. Specifically, the normal saline contains NaCl, which is a salt, and the glycerol reads on at least one polyhydroxy compound. Normal saline has a pH of about 5.5, which satisfies the limitation the solution has a pH ranging from about 4.0 to about 7.5.
The final glycerolized ADM samples within the final 85% glycerol normal saline solution of Sun et al differ from the instant claimed composition in that Sun et al does not teach inclusion of a biocompatible buffer.
In Example 2 Sun et al uses normal saline as the aqueous solvent. However, Sun et al teach several options for aqueous solvents usable in the WRA-containing solution, including, inter alia, PBS or Ringer’s lactate, both of which are considered biocompatible buffers, and also include salts (PBS contains NaCl, KCl, Na2HPO4, KH2PO4 (See Millipore Sigma “1X Phosphate-Buffered Saline (PBS) Recipe Calculator”); Ringer’s lactate contains NaCl, CH3CH(OH)COONa; KCl and CaCl2-2H2O (See B Braun Medical Inc)). Based on the disclosure of Sun et al, it would have been prima facie obvious to have substituted either of PBS or Ringer’s lactate as the aqueous solvent in the method of Example 2. This conclusion is based on the teaching of Sun et al that normal saline, PBS and Ringer’s lactate are all examples of suitable aqueous solvents which can be present in the solution containing the WRA, and because Sun et al teaches them as alternatives for the same purpose. PBS has a pH of about 7.4. Ringers lactate has a pH of about 6.5. Thus, substitution of either would still satisfy the limitation the preservation solution has a pH in the range of about 4.0 to about 7.5. Both pH 7.5 and pH 6.5 are considered to read on pH about 5.4 to about 6.0 (claim 20).
Regarding claims 2 and 3: Following the discussion of claim 1 above, Sun et al differs from claims 2 and 3 that Sun et al doesn’t teach or suggest use of a citric acid buffer or a citric acid buffer in combination with a phosphate buffer.
However, at the time the invention was made there were a finite number of buffers known in the art, including citric acid buffers, each with predictable buffering capabilities around known pH and pKa (See Millipore Sigma “Buffering Reference Guide”). Thus, it would have been obvious to a person of ordinary skill in the art to try any known buffer or combination of known buffers that would serve as a solvent for glycerol and have the ability to buffer in the pH range of about 5.5 to 7.4 (the pH range covered by the solvent solutions specifically identified by Sun et al). At least Na2HPO-4 buffer preparation (pH 2.6-7.6) and Sodium citrate buffer preparation (pH 3.0-6.2) were amongst the known buffers available at the time the invention was made, and known to buffer within the range of 5.5 to 7.4. The effect of buffering agents was predictable at the time the invention was made. Therefore, it would haven prima facie obvious to try these citric acid buffers, alone or in combination with any other known buffer, in the method of Sun et al to perform the ‘water-replacing method’. It has been held that "a person with ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense." See KSR International Co. v Teleflex, Inc. 82 USPQ2d 1385 at 1390.
Regarding claim 4: At least PBS is a phosphate buffer.
Regarding claims 5 and 6: Both of PBS and Ringer’s lactate include salt NaCl. PBS contains approximately 103 mM NaCl, and Ringer’s lactate contains approximately 137 mM NaCl, both of which satisfy the limitation salt at a concentration of up to about 150MM in the preservation solution (solution comprising WRA).
Regarding claim 7 and 13: The glycerol, per se, reads on at least one polyhydroxy compound ...which can be considered a tissue stabilizer.
Regarding claims 7 and 14-19: Example 2 of Sun et al differs from some embodiments of claim 7 in that the composition of Example 2 does not teach including an additional biocompatible co-solute in the ‘solution comprising WRA’.
However, Sun et al teach that additional supplemental agents that serve to prevent or minimize damage that can occur to ATM during storage and/or sterilization can further be included. Sun et al teaches such additional supplemental agents can include, inter alia, sugar alcohols, such as mannitol and sorbitol (See ¶0063). Based on this teaching of Sun et al, it would have been prima facie obvious to one having ordinary skill in the art, at the time the invention was made, to further modify the preservation solution of Sun et al (modified as discussed regarding claim 1) to include additional sugar alcohols, such as mannitol and/or sorbitol. One would have been motivated to include the additional sugar alcohols because Sun et al teaches they are examples of additional agents that can further assist in protection/preservation of the tissue. Both mannitol and sorbitol satisfy the limitation of a polyhydroxy compound comprising a tissue stabilizer and/or a biocompatible co-solute (reading on claims 7, 16 and 17). Determination of the optimal amount of sugar alcohol in the ‘solution comprising WRA’ would have been a matter of routine optimization which would have been well within the purview of the artisan of ordinary skill. The concentration would depend on the tissue of the ATM, the volume of the ATM, and the presence and type of additional WRAs/supplementary agents. The concentrations recited by claims 14, 15, 18 and 19 are thus considered prima facie obvious.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-54 of U.S. Patent No. 8735054.
Although the claims at issue are not identical, they are not patentably distinct from each other because the current claims are considered to be an obvious variation on the patented claims.
Patented claim 1 discloses a composition comprising an acellular tissue matrix and a solution, wherein the solution comprises a biocompatible buffer, a salt, a surfactant, a tissue stabilizer, and a biocompatible solute. Dependent claims 2-4 define the biocompatible buffer as being the same buffer as required by instant claims 2-4. Dependent claim 5 defines the salt as being sodium chloride in a concentration of up to 150 mM (which falls within the range required by instant claim 6). Dependent claim 6 defines the surfactant as TWEEN 20 or TWEEN 80, each of which are examples of at least one polyhydroxy compound. Dependent claims 7-8 define the metal chelator as EDTA or EGTA, each of which are examples of at least one polyhydroxy compound. Dependent claim 9 defines the tissue stabilizer as glycerol, which is a polyhydroxy compound. Dependent claims 10-12 define the biocompatible solute as trehalose or mannitol, each of which are polyhydroxy compounds.
Regarding instant claims 1, 2, 4-12, 14, and 16-20: At least patented claim 20 anticipates these claims, noting that the citrate reads on a biocompatible buffer, specifically a citrate buffer; sodium chloride reads on a salt, and is present at a concentration of 100 mM (which is less than 150 MM); TWEEN 20 reads on a polyhydroxy compound, a surfactant and specifically a non-ionic surfactant, it is present in an amount of 0.2% (w/v) (which is about 0.2% w/v or less); EDTA reads on a polyhydroxy compound, and a metal chelator, it is present at a concentration of about 2 mM (which is with the range of about 1 mM to about 50 mM); glycerol reads on a polyhydroxy compound, and a tissue stabilizer, and is present in an amount of about 10% (w/v); and trehalose reads on a polyhydroxy compound and a biocompatible solute, and is present at a concentration of 200 mM (which is about 1 M or less, and equates to about 6.8% w/v, which is about 20% w/v or less) . The solution has a pH of about 5.4, which is within the claimed range of 4.0 to 7.5, as well as 5.4 to 6.0.
Regarding instant claims 3 and 4: At least patented claims 3 and 4 teach the biocompatible buffer can alternatively be an acetate buffer, a citrate buffer, a phosphate buffer, or a combination thereof. This disclosure renders obvious a variation of the solution of patented claim 20 that includes any one or more of the buffers disclosed in patented claims 3 and 4, as they are taught as alternatives substitutable for one another.
Regarding instant claims 8 and 9: At least patented claim 6 teaches the surfactant can be either of TWEEN 20 or TWEEN 80. Patented claim 32 further teaches the other non-ionic surfactants claimed in current claim 9. The disclosure of the various non-ionic surfactants within the patented claims renders obvious a variation of the solution of patented claim 20 that includes any one or more of the non-ionic surfactants recited by patented claims 6 and 32, as they are taught as alternative non-ionic surfactant substitutable for one another.
Regarding instant claim 11: At least patent claim 8 teaches the metal chelator can be EGTA, patent claim 38 teaches suitable metal chelator also include DMSA and DTPA. The disclosure of the various metal chelator within the patented claims renders obvious a variation of the solution of patented claim 20 that includes any one or more of the metal chelator recited by patented claims 8 or 38, as they are taught as alternatives substitutable for one another.
Regarding claim 13: At least patent claim 36 teaches poly-glycerol, propylene glycol, polyethylene glycol and polyvinyl alcohol are alternative tissue stabilizers to glycerol. The disclosure of the various tissue stabilizer within the patented claims renders obvious a variation of the solution of patented claim 20 that includes any one or more of the tissue stabilizers recited by patented claim 36, as they are taught as alternatives substitutable for one another.
Regarding claim 15: Patented claim 1 permits for the tissue stabilizer to be present in an amount of up to 10% w/v. The molarity of this will depend on the exact tissue stabilizer used. Modification of the concentration to achieve optimal tissue stabilization would have been a matter of routine optimization and is not considered inventive.
Regarding claim 17: At least patented claim 10 states the biocompatible co-solute can be any sugar or sugar alcohol. Patented claim 12 states the sugar alcohol can be mannitol. Patented claim 25 teaches the biocompatible co-solute can be trehalose, mannitol, sorbitol, xylitol, erythritol, arabitol, isomalt, maltitol and/or lactitol. The disclosure of the various sugar alcohols within the patented claims renders obvious a variation of the solution of patented claim 20 that includes any one or more of the sugar alcohols recited by patented claim 12 or 25, as they are taught as alternatives substitutable for one another.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over each of:
claims 1-38 of U.S. Patent No. 9150318,
claims 1-41 of U.S. Patent No 10322835, and
claims 1-34 of U.S. Patent No 10906679.
Although the claims at issue are not identical, they are not patentably distinct from each other because the current claims are considered to be an obvious variation on the patented claims.
The claims of each patent are directed to methods for sterilizing a tissue matrix, the method involves, inter alia, providing an acellular collagen-based tissue matrix; contacting the acellular collagen-based tissue matrix with a first solution comprising peracetic acid (PAA); and then contacting the acellular collagen-based tissue matrix with a protective solution effective to stabilize the tissue matrix during and after exposure to irradiation. The protective solution reads on, or is an obvious variation of, the solution of the instant claims (See below). Therefore, in carrying out the method of the patented claims, one would inherently produce a composition which reads on the composition of instant claims 1-20.
The protective solution is recited in claims 22-38 of US Patent 9150318, claims 23-38 of US Patent 10322835, and claims 1 and 14-34 of US Patent 10906679. In all patents, the protective solutions contain a biocompatible buffer, a salt, a transition metal chelator, a tissue stabilizer, and a biocompatible solute, and have a pH of between 5.2 and 6.9. The patent claim sets define each of the components as being those required by the instant claims, and at concentrations that fall within or overlap with the ranges of the instant claims. The fact that the various chemicals are disclosed as alternatives within the patent claims renders obvious selection of any of the agents within the patent claim scope.
Conclusion
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/ALLISON M FOX/ Primary Examiner, Art Unit 1633
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