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 .
Claims 1-7 are under examination.
Response to Applicant’s Amendments/Arguments
The claims have been amended. The former rejections have been modified to address the new claim limitations. The arguments are addressed under each of the rejections. Because the specification was amended, the specification objection has been withdrawn.
Claim Interpretation
The specification fails to define “dynamic” or “dynamic perfusion.” Therefore, the term “dynamic” will be given the broadest reasonable interpretation. According to the Merriam Webster Dictionary, “dynamic” means “marked by usually continuous and productive activity or change”.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4, 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Zal (WO 2019201863) in view of Hashimoto (CA 3133779) and Goldstein (US 7,129,035). For applicant’s convenience, Zal (US 20210172900) will be used as an English translation for Zal (WO 2019201863).
Zal teaches a colloidal aqueous solution that can be perfused/permeate the tissue such as lung tissue and be used for storage purposes (Paragraphs 131-142 of Zal). This solution can contain the following components: hydroxyethyl starch at a concentration range of between 1 and 50 g/l; hydroxyethyl starch is an option that can be used instead of human serum albumin (Paragraph 142 of Zal). Furthermore, other well-known perfusion solutions include 50 g/L of hydroxyethyl starch in their formulations (Paragraphs 45 and 128 of Zal). Paragraphs 131 to 142 of Zal further disclose osmotic agents (glucose and raffinose), a buffer system (KH2PO4 is a buffer), and electrolytes (magnesium chloride). Zal’s solution has a pH of between 6.5 and 7.6 (Paragraph 131). Zal’s solution has an osmolarity between 250 and 350 mOsm/L (Paragraph 144 of Zal). The solution of Zal is used with a process/system involving frequent monitoring of parameters such as changing oxygen levels during perfusion (Abstract of Zal); therefore, Zal’s perfusion solution would be considered adequate for a dynamic/changing perfusion process as in instant Claims 1 and 2.
Zal does not teach the inclusion of dextran and EDTA. However, Hashimoto teaches that a preservation solution can include dextran at a concentration of 5 g/L (Page 20) and EDTA (Paragraph 24 of Hashimoto). It would have been obvious to an artisan of ordinary skill at the time of effective filing to have included dextran and EDTA in the aqueous solution of Zal. An artisan would have been motivated to have included dextran and EDTA into the solution of Zal because these components help to promote cell viability (Pages 20 and 24). There would have been a high expectation for success because Hashimoto teaches that dextran and EDTA can improve cell viability (Pages 20 and 24). as in instant Claim 1.
Zal teaches maintaining organ/tissue in sterilized conditions but does not further elaborate on how this sterilization can be accomplished. However, Goldstein teaches that it’s preservation solution can be composed of sterile components (Paragraph 74-75) and the solution when combined with the tissue/organ can be further sterilized (Paragraph 61-62). It would have been obvious to an artisan of ordinary skill in the art to have sterilized the components of the solution with the organ/tissue using irradiation so that the sterilized tissue/organ could later be used as a treatment (Paragraph 17 of Goldstein). Goldstein further teaches adding antioxidants such as sodium metabisulfite to an organ preservation solution in order to protect against harmful radicals produced from sterilization techniques used (Paragraph 46 Goldstein). There would have been a high expectation for success because Goldstein teaches that sterilization can protect solution and/or tissue from unwanted contamination (Paragraph 17 of Goldstein). Although Zal includes antioxidants in his mediums, he does not teach using sodium metabisulfite specifically. An artisan would have been motivated to have used sodium metabisulfite because it can protect cells, tissue, and/or organs (Paragraph 46 of Goldstein). Because sodium metabisulfite can be used to protect cells, tissue, and/or organs in solution, there would have been a high expectation for success (Paragraph 46 of Goldstein) as in instant Claim 1.
Dependent Claims taught by Hashimoto
Hashimoto teaches that dextran is present at a concentration of 5 g/L (Page 20) as in instant Claim 3. Hashimoto teaches incorporating sodium chloride (Paragraph 50) as in instant Claim 4. Hashimoto teaches including electrolytes such as potassium chloride and sodium chloride (Page 50) as in instant Claim 6.
Dependent Claims taught by Goldstein
Goldstein teaches that the salt/electrolyte used can be sodium chloride and that the concentration of chlorinated salts is 0.02 to .5 M (Paragraph 30) which encompasses the range recited in instant Claims 6-7.
Zal teaches a composition that can be used to preserve tissue including lung tissue. Zal fails to expressly state that the solution contains dextran and EDTA. However, an artisan would have been further motivated to have included dextran and EDTA because they are used in solutions that boost cell viability as taught in Hashimoto. Although Zal hints at sterilization, Goldstein expressly discusses sterilization at length. An artisan would have been motivated to have sterilized the solution and the tissue/organ within in order to sterilize the tissue/organ and its environment. An artisan would have been further motivated to have included antioxidants in the solution since antioxidants protect tissue against harmful radicals as taught by Goldstein. Given the teachings of the cited references and the level of skill of an ordinary skilled artisan at the time of applicant’s invention, it must be considered, absent evidence to the contrary, that the ordinarily skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
All of the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention (See KSA International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007)). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.'s and Ph.D.'s. They will be medical doctors, scientists, or engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in molecular biology, immunology, and organ perfusion and storage technology. Therefore, the level of ordinary skill in this art is high.
Response to Applicant’s Arguments
Applicant argues the following:
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The terms “dynamic” or “dynamic perfusion” are not specifically defined in the specification. Therefore, the term “dynamic” will be given the broadest reasonable interpretation. The Merriam Webster dictionary defines dynamic as “marked by usually continuous and productive activity or change.” In the primary Zal reference, the organ tissue is perfused in a solution and oxygen levels are being continuously monitored for change in O2 levels surrounding the tissue/organ. Therefore, Zal does indeed teach a dynamic perfusion process. Furthermore, the instant set of claims are composition claims and not a method of actively perfusing solution using a pump through a tissue under various conditions. The intended use phrase fails to add additional structures to the claimed composition.
Applicant further argues that, “dynamic preservation involves continuous circulation of the solution through the organ using a pump, allowing functional evaluation of the lung before implantation.” The instant claims do not require a pump and the claims are not method claims for carrying out perfusion with a pump.
Applicant further agues
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As argued above, the term dynamic is not defined in the specification so it can be given the broadest reasonable interpretation. As argued above, Zal teaches a perfusion process in which oxygen concentrations can be continuously monitored for change. Therefore, Zal can be considered to teach a dynamic prefusion process. Furthermore, the preferred solution of Zal can contain, “”at least one compound chosen from hydroxyethyl starch, polyethylene glycols of different molecular weight and human serum albumin (Paragraph 142 of Zal).” Only one such compound needs to be chosen which can include hydroxyethyl starch by itself. Therefore, Zal teaches a perfusion solution that does not contain human serum albumin.
Applicant argues the following, “the invention therefore defines a colloidal solution capable of maintaining oncotic pressure, similar to albumin during dynamic lung perfusion in EVLP procedures, protecting the lung during evaluation.” As mentioned before, the instant claims recite a collection of ingredients in a composition. The term dynamic can be defined broadly to include a type of perfusion solution that involves change; the Zal reference satisfies this requirement because it monitors changing oxygen levels.
Applicant also argues the secondary references cited in the rejection.
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An artisan would have still been motivated to have included the EDTA of Hashimoto and the sodium metabisulfite of Goldstein since such components provide protection to a perfused tissue. An artisan would have been motivated to have added such components because they provide protection to perfused tissue.
Applicant further argues, “The claimed solution also provides an isotonic environment comparable to blood, maintains an optimal pH for cell protection, and provide antioxidants and energy substrates to support cellular metabolism.” An isotonic environment comparable to blood is not mentioned in the instant claims. The references cited teach the required pH, antioxidants, and energy substrates as cited in the rejections.
Claims 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over Zal (WO 2019201863) in view of Hashimoto (CA 3133779), Goldstein (US 7,129,035), Bancel (US 20130165504). For applicant’s convenience, Zal (US 20210172900) will be used as an English translation for Zal (WO 2019201863).
Zal, Hashimoto, and Goldstein apply as above to teach claims 1-4,6-7. Zal teaches that the pH of the solution can be maintained at a pH between 6.5 to 7.4 and includes buffers in its solution (Paragraphs 131-142 of Zal). However, Zal fails to teach using sodium phosphate monobasic dehydrate and/or sodium bicarbonate as a buffer in Zal’s solutions. Bancel teaches that monobasic sodium phosphate and sodium bicarbonate can be successfully used as buffers in solutions exposed to cells/tissue/organs (including lung tissue) (Paragraph 556 of Bancel). It would have been obvious to an artisan of ordinary skill at the time of effective filing to have used the buffer agents taught in Bancel in the preservation solution of Zal. An artisan would have been motivated to have used the buffer agents of Bancel because they are able to successfully buffer the solution and protect the tissue/organ that lies within the solution (Paragraph 556 of Bancel). Because Bancel teaches that a phosphate monobasic dehydrate and sodium bicarbonate can effectively serve as buffers in solution containing living tissue, there would have been a high expectation for success (Paragraph 556 of Bancel) as in instant Claim 5.
Zal teaches a composition that can be used to preserve tissue including lung tissue. Zal fails to expressly state that the solution contains dextran and EDTA. However, an artisan would have been further motivated to have included dextran and EDTA because they are used in solutions that boost cell viability as taught in Hashimoto. Although Zal hints at sterilization, Goldstein expressly discusses it at length. An artisan would have been motivated to have sterilized the solution and the tissue that it carries in order to provide sterilized tissues/cells placed within the solution, allowing the tissue to be used for therapeutic purposes. An artisan would have been further motivated to have included antioxidants in the solution since it protects tissue against harmful radicals. Goldstein also teaches the use of antioxidants to protect tissue from unwanted damage from free radicals. Bancel teaches different cell/tissue/organ friendly antioxidants that can be used to successfully balance pH levels. An artisan would have been motivated to have used such buffers because they can safely adjust the pH levels of solutions that surround tissues/organs. Given the teachings of the cited references and the level of skill of an ordinary skilled artisan at the time of applicant’s invention, it must be considered, absent evidence to the contrary, that the ordinarily skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
All of the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention (See KSA International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007)). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.'s and Ph.D.'s. They will be medical doctors, scientists, or engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in molecular biology, immunology, and organ perfusion technology. Therefore, the level of ordinary skill in this art is high.
Response to Argument against Bancel
Applicant argues that Bancel is deficient because Zal is defective. As argued above, Zal is not defective; therefore, Bancel is not deficient.
Conclusion
All claims stand rejected.
Applicant’s amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN K VAN BUREN whose telephone number is (571)270-1025. The examiner can normally be reached M-F:9:30am-5:40pm; 9:00-10:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached at 571-272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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LAUREN K. VAN BUREN
Examiner
Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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