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 .
Information Disclosure Statement
The information disclosure statement filed 2/11/26 fails to comply with 37 CFR 1.98(a)(3)(i) because it does not include a concise explanation of the relevance, as it is presently understood by the individual designated in 37 CFR 1.56(c) most knowledgeable about the content of the information, of each reference listed that is not in the English language. It has been placed in the application file, but the information referred to therein has not been considered.
The Office Action from the Japanese Patent Office dated 2/9/26 has no translation.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-6, 10, 12-13, 28 and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Margraf (US 2012/0107829) in view of Onodera (US 2002/0044884).
Regarding claim 1, Margraf (US 2012/0107829) teaches a method of protecting biological activity of a biologically active molecule against radiation damage during radiation sterilization (abstract, p0016-p0017), comprising:
(a) contacting the biologically active molecule in an aqueous solution with a radioprotectant composition comprising at least one soluble radioprotectant compound to obtain a radioprotected mixture prior to radiation sterilization (biomolecules are mixed with a soluble radioprotectant composition of amino acids in an aqueous solution in order to embed the biomolecules with the radioprotected composition, p0084, p0085); and
(b) radiation sterilizing the radioprotected mixture (the mixture is radiation sterilized, p0106), wherein biological activity of the biologically active molecule in the radioprotected mixture after radiation sterilization is greater than biological activity of a control sample of the biologically active molecule that is radiation sterilized without the radioprotectant compound present, and thereby protecting biological activity of the biologically active molecule against radiation damage during radiation sterilization (Experiment 1 shows the testing of protected biomolecules obtained through the method disclosed above, wherein the radioprotectant composition comprises cysteine (par. 14). The biomolecules coated with at least two radioprotectants show greater biological activity than unprotected biomolecules. Fig. 2, p0220-p0225). Margraf appears to be silent with regards to the biologically active molecule comprising a mitogen or a biologically active imidozoquinoline having TLR agonist activity, or (iii) a mitogen and a biological active imidozoquinoline having TLR agonist activity.
Onodera discloses a sterilization method in which a biologically active substance is protected by a sterilizing-protecting agent wherein its biological activity is exhibited even after sterilization (p0006). Onodera further discloses the method comprising contacting the biologically active molecule in an aqueous solution with the at least one sterilizing-protecting agent in order to coat the to-be- sterilized biologically active substance (p0021). Further, Onodera teaches wherein the biological activity comprises a mitogenic lectin (biologically active substance can be a pokeweed mitogen and kidney bean lectin, par. 30). It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the method disclosed by Margraf such that the biologically active molecule comprises a mitogen as disclosed by Onodera to arrive at the claimed invention. One would have been motivated to do so in order to use a known means for protecting biologically active molecules to protect mitogens, a useful biologically active molecule which are known to be in need of sterilization protection as set forth by Onodera. The combination of familiar prior art elements to perform the same functions together as they do separately, including mitogens and radioprotectant means for protecting them from radiation, according to known means to arrive at results that are nothing more than predictable is prima facie obvious. MPEP 2143(I)(A).
Regarding claim 2, Margraf further teaches the radioprotected mixture is dried prior to the step of radiation sterilizing (after contacting the biomolecules with the radioprotectant and prior to sterilizing, a drying step is performed, p0096- p0097).
Regarding claim 3, Margraf teaches –
a method of protecting a plurality of molecules of a biologically active molecule against a loss of biological activity from said plurality of molecules during a period of time in storage (abstract, p0016-p0017), comprising:
(a) contacting the biologically active molecule in an aqueous solution with at least one soluble radioprotectant compound to obtain a radioprotected mixture prior to radiation sterilization (biomolecules are mixed with a soluble radioprotectant composition of amino acids in an aqueous solution in order to embed the biomolecules with the radioprotected composition, p0084, p0085);
(b) drying the radioprotected mixture to obtain a dried radioprotected mixture (after contacting the biomolecules with the radioprotectant and prior to sterilizing, a drying step is performed, p0096- p0097);
(c) radiation sterilizing the dried radioprotected mixture (the mixture is radiation sterilized, p0106); and
(d) storing the dried radioprotected mixture for a period of time to obtain a stored dried radioprotected mixture (may be stored until needed, p0107), wherein biological activity of the biologically active molecule in the stored dried radioprotected mixture after radiation sterilization and storage for said period of time is greater than biological activity of a control sample of the biologically active molecule that is dried, radiation sterilized without the radioprotectant compound present, and then stored for the period of time, and thereby protecting a plurality of molecules of the biologically active molecule against loss of biological activity during the period of time in storage (Experiment 1 shows the testing of protected biomolecules obtained through the method disclosed above, the radioprotectant composition comprises cysteine (par. 14). The biomolecules coated with at least two radioprotectants show greater biological activity than unprotected biomolecules after a period of time. Fig. 2, p0220-p0225). Margraf appears to be silent with regards to the biologically active molecule comprising a mitogen or imidazoquinoline.
Onodera discloses a sterilization method in which a biologically active substance is protected by a sterilizing-protecting agent wherein its biological activity is exhibited even after sterilization (p0006). Onodera further discloses the method comprising contacting the biologically active molecule in an aqueous solution with the at least one sterilizing-protecting agent in order to coat the to-be- sterilized biologically active substance (p0021). Further, Onodera teaches wherein the biological activity comprises a mitogenic lectin (biologically active substance can be a pokeweed mitogen and a kidney bean lectin, par. 30). It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the method disclosed by Margraf such that the biologically active molecule comprises a mitogen as disclosed by Onodera to arrive at the claimed invention. One would have been motivated to do so in order to use a known means for protecting biologically active molecules to protect mitogens, a useful biologically active molecule which are in need of sterilization protection as established by Onodera. The combination of familiar prior art elements to perform the same functions together as they do separately, including mitogens and radioprotectant means for protecting them from radiation, according to known means to arrive at results that are nothing more than predictable is prima facie obvious. MPEP 2143(I)(A).
Regarding Claim 4, Margraf teaches –
a method of protecting biological activity of a biologically active molecule against radiation damage during radiation sterilization (abstract, p0016-p0017), comprising:
(a) contacting the biologically active molecule in an aqueous solution with at least one soluble radioprotectant compound to obtain a radioprotected mixture prior to radiation sterilization (biomolecules are mixed with a soluble radioprotectant composition of amino acids in an aqueous solution in order to embed the biomolecules with the radioprotected composition, p0084, p0085);
(b) drying the radioprotected mixture to obtain a dried radioprotected mixture (after contacting the biomolecules with the radioprotectant and prior to sterilizing, a drying step is performed, p0096- p0097); and
(c) radiation sterilizing the dried radioprotected mixture to obtain a dried radiation sterilized radioprotected mixture (the mixture is radiation sterilized, p0106), wherein, following rehydration of the dried radiation sterilized radioprotected mixture to obtain a rehydrated radiation sterilized radioprotected mixture, biological activity of the biologically active molecule in the radioprotected mixture after radiation sterilization is greater than biological activity of a control sample of the biologically active molecule that is radiation sterilized without the radioprotectant compound present, and thereby protecting biological activity of the biologically active molecule against radiation damage during radiation sterilization (The dried radiation sterilized radioprotected mixture can be rehydrated in body liquids prior to use, p0135. Further, Example 1 uses ELISA diagnostic applications in which the dried and incubated sterilized radioprotected mixture is rehydrated with a solution used to detect biological activity. Results showing the biomolecules coated with at least two radioprotectants show greater biological activity than unprotected biomolecules. Fig. 2, p0220-p0225), the radioprotectant composition comprises cysteine (par. 14).
Margraf appears to be silent with regards to the biologically active molecule comprising a mitogen or imidazoquinoline.
Onodera discloses a sterilization method in which a biologically active substance is protected by a sterilizing-protecting agent wherein its biological activity is exhibited even after sterilization (p0006). Onodera further discloses the method comprising contacting the biologically active molecule in an aqueous solution with the at least one sterilizing-protecting agent in order to coat the to-be- sterilized biologically active substance (p0021). Further, Onodera teaches wherein the biological activity comprises a mitogen having mitogenic activity (biologically active substance can be a pokeweed mitogen and a kidney bean lectin, par. 30). It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the method disclosed by Margraf such that the biologically active molecule comprises a mitogen as disclosed by Onodera to arrive at the claimed invention. One would have been motivated to do so in order to use a known means for protecting biologically active molecules to protect mitogens, a useful biologically active molecule in need of sterilization protection as set forth in Onodera. The combination of familiar prior art elements to perform the same functions together as they do separately, including mitogens and radioprotectant means for protecting them from radiation, according to known means to arrive at results that are nothing more than predictable is prima facie obvious. MPEP 2143(I)(A).
Regarding claim 5, modified Margraf further teaches the biologically active molecule comprises a mitogenic lectin (see the rejection of claim 1 above).
Regarding claim 6, modified Margraf further teaches the mitogen is a pokeweed mitogen (par. 30 discloses PWM which appears to be misspelled as “pork weed” mitogen which is not a known type of mitogen and PWM is the common acronym for the substance).
Regarding claim 10, Margraf further teaches the radioprotectant compound is present in the radioprotectant mixture at 200 millimolar (par. 220), anticipating the claimed range of at least 50 millimolar.
Regarding claim 12, modified Margraf further teaches the mitogenic lectin has lymphocyte proliferation inducing activity (the mitogens disclosed by Onodera include lymphocyte proliferation inducing activity by nature of their activity with lymphocytes).
Regarding claim 13, modified Margraf further teaches the lymphocyte proliferation activity comprises T-cell proliferation inducing activity (protecting the biological activity of a mitogen capable of exhibiting T-cell proliferation inducing activity would necessarily include the protection of the same, and the activation or implementation of the activity itself is not claimed and therefore Margraf teaches this limitation).
Regarding claims 28 and 31, modified Margraf discloses the radioprotectant composition includes at least one dipeptide or tripeptide (claim 10) where the peptides are the same or different and the composition preferably includes one amino acid (pars. 21, 52, 69) where the amino acid is selected from the group including cysteine, histidine, melatonin (par. 14, 69). It therefore would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the method disclosed by modified Margraf such that the radioprotectant composition consists essentially of cysteine, histidine, or cysteine and histidine to arrive at the claimed invention. One would have been motivated to do so to use the suggested amino acids for their suggested purpose of stabilizing and protecting biomolecules as disclosed by Margraf to arrive at a simple and effective bioprotectant composition.
Regarding specifically the limitation in claim 31 that the radioprotectant includes essentially cysteine and histidine: Margraf discloses the radioprotectant may include two different amino acids (see claim 10, par. 69), and the amino acids include are selected from the group including cysteine and histidine (par. 14, 69). Therefore, It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the method disclosed by Margraf such that the radioprotectant includes essentially cysteine and histidine to arrive at the claimed invention. One would have been motivated to do so to use the suggested amino acids for their suggested purpose of stabilizing and protecting biomolecules as disclosed by Margraf to arrive at a simple and effective bioprotectant composition.
Claims 11 and 14 is rejected under 35 U.S.C. 103 as being unpatentable over Margraf (US 2012/0107829) in view of Onodera (US 2002/0044884) as applied to claim 1 above, and further in view of Raz (US 2005/0175630).
Regarding claim 11, modified Margraf is set forth with regards to claim 1 above but appears to be silent with regards to the biologically active molecule includes biologically active imidazoquinoline.
Raz (US 2005/0175630) discloses a biologically active imidazoquinoline including resiquimod is included in a mixture that is radiation sterilized (par. 155, 102), and therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the method disclosed by modified Margraf to use a radioprotectant composition to protect a biologically active molecule including resiquimod to arrive at the claimed invention. One would have been motivated to do so to use a known method of protecting biologically active molecules from radiation on a useful biologically active molecule that is known to be used in tandem with radiation to avoid negatively deactivating the biologically active molecule to arrive at an improved method. The combination of familiar prior art elements, including methods of radioprotection and molecules in need of protection, according to known means for the same purpose together as separate and to arrive at results that are nothing more than predictable is prima facie obvious. MPEP 2143(I)(A).
Regarding claim 14, modified Margraf is set forth above with regards to claim 1 but appears to be silent with regards to the biologically active molecule includes biologically active imidazoquinoline including imiquimod, gardiquimod, or resiquimod.
Raz (US 2005/0175630) discloses a biologically active imidazoquinoline including resiquimod is included in a mixture that is radiation sterilized (par. 155, 102), and therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the method disclosed by modified Margraf to use a radioprotectant composition to protect a biologically active molecule including resiquimod to arrive at the claimed invention. One would have been motivated to do so to use a known method of protecting biologically active molecules from radiation on a useful biologically active molecule that is known to be used in tandem with radiation to avoid negatively deactivating the biologically active molecule to arrive at an improved method. The combination of familiar prior art elements, including methods of radioprotection and molecules in need of protection, according to known means for the same purpose together as separate and to arrive at results that are nothing more than predictable is prima facie obvious. MPEP 2143(I)(A).
Response to Arguments
Applicant's arguments filed 12/16/25 have been fully considered but they are not persuasive.
Applicant’s remarks directed towards claims 1, 3, and 4 arguing Margraf fails to teach or fairly suggest the limitation that the radioprotectant composition comprises cysteine are not persuasive.
Applicant argues on page 7 that the references do not teach cysteine as a radioprotectant, however par. 14 of Margraf explicitly discloses cysteine as a useful component of the protecting composition. Applicant points to par. 61 arguing the reference teaches away from cysteine as the amino acid can cause discoloration. However, in that same paragraph Margraf explicitly discloses that the effect of discoloration should not discourage the use of cysteine as a radioprotectant.
Applicant’s remarks directed towards Onodera are not persuasive because Onodera is not relied upon for teaching the use of cysteine.
Applicant’s remarks directed towards the Affidavit filed 12/16/25 are further not persuasive. Applicant argues in view of the Affidavit that cysteine is uniquely effective as a radioprotectant, which does not undermine the combination of Margraf and Onodera to arrive at the claimed invention. Margraf indeed suggests the use of cysteine as a radioprotectant, and the contents of the affidavit would only support that teaching further.
The affidavit further states that Margraf teaches the use of various amino acid configurations, which further does not undermine the teaching of Margraf that cysteine is a desirable radioprotectant to use with the methods disclosed in the reference. The reference teaching many amino acids does not undermine the teaching of a specific one as is the case in paragraph 14 of Margraf. Claims 1, 3, and 4 remain rejected.
Applicant’s remarks directed towards the remaining claims are not persuasive as Applicant does not attack the references for any of the reasons the references are used in the rejection above. The remaining claims remain rejected similarly.
Conclusion
THIS ACTION IS MADE FINAL. 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.
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/BRENDAN A HENSEL/Examiner, Art Unit 1758