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 . 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.
Election/Restrictions
Applicants elected a formulation comprising magnetite particles attached to INA using APTES as a linker and glutaraldehyde as a crosslinking agent without traverse in the reply filed on 24 June, 2025.
Claims Status
Claims 1-11 are pending.
Claim 1 has been amended.
Claims 6, 7, and 10 have been withdrawn due to an election/restriction requirement.
Withdrawn Rejections
The rejection of claims 1-5, 8, 9, and 11 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite due to uncertainty as to the interpretation of “crosslinker” is hereby withdrawn due to amendment.
The rejection of claims 1-5, 8, 9, and 11 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite due to uncertainty as to what constitutes an INA is hereby withdrawn due to argument.
Maintained/Modified Rejections
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
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.
Claim 9 requires that the material be a cooling additive. However, upon nucleation, supercooled water will heat up to the freezing point of water due to the heat of fusion (Kobiyashi et al, Cryobiol. (2016) 72 p216-224, p216, 2nd column, 2nd paragraph, continues to p217, 1st column, 1st paragraph). With a nucleating site, the water does not become supercooled, but does not become cooler than the water otherwise would be (compare fig 1A, cooling curve of purified water with supercooling to fig 1B, cooling of water with a nucleator). This makes it unclear how the material is used as a cooling additive; if there needs to be something in addition to the construct itself. For purpose of examination, this will be considered an intended use with the limitation met by the construct.
response to applicant’s arguments
Applicants argue that a person of skill in the art would interpret “cooling additive” as a nucleating agent or freezing promotor.
Applicant's arguments filed 16 Jan, 2026 have been fully considered but they are not persuasive.
Applicants have not defined “cooling additive,” which means the plain meaning of the term is used (MPEP 2111.01(I)). The plain meaning of the term is an additive that cools what it is placed into, which is not how applicants say it should be interpreted, and is confusing scientifically. However, applicant’s definition of the term in their arguments is not supported by their disclosure or any cited references.
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.
Claim(s) 1-5, 8, 9, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Mie et al (US 7,700,718, cited by applicants) in view of Kobayashi et al (PNAS (2018) 15(21) p5383-5388) and Feng et al (Chem. Eng. J. (2016) 286 p216-222, cited by applicants). Note that Kobiyashi et al is a different reference than Kobiyashi et al used in the indefiniteness rejection, above.
Mie et al discuss materials for promoting the freezing of water (title). This is done with a material with ice nucleation activity to make ice (3d column, lines 16-21) by attaching polypeptides on a carrier (column 3, line 22-28). The requirement is that the polypeptide have side chains that bind to water (column 4, line 66-column 5, line 8). A protein that appears to match applicant’s description of an INP is mentioned (compare column 2, line 57-67 with p2, 2nd paragraph of applicant’s specification), and various enzymes are mentioned (column 5, line 32-40). Attachment can be by any known method (column 11, line 1-2), with silanes and glutaraldehyde (column 13, line 22-29). The carrier can be in the form of nanoparticles (column 13, line 58).
The difference between this reference and the claims is that this reference does not clearly discuss the linking chemistry, and uses a substrate different than applicant’s elected species.
Kobiyashi et al discusses ice nucleation with nanophase magnetite (title). This is a strong ice nucleator; very low levels of the material will nearly eliminate supercooling (p5383, 2nd column, 2nd paragraph). This reference states that magnetite nanoparticles are powerful ice nucleators.
Feng et al discuss the attachment of an aminoacylase on magnetite (title). The particles were formed in water, separated from the reaction solution with a magnet, washed several times, resuspended in 50% ethanol, and mixed with APTES, applicants’ elected silane (p217, 2nd column, 1st paragraph). The material was isolated and resuspended in PBS, then reacted with glutaraldehyde, washed, and mixed with the enzyme (p217, 2nd column, 2nd paragraph, continues to p218, 1st column, 1st paragraph). This reference discusses attachment of a polypeptide to a magnetite particle using APTES and glutaraldehyde.
Therefore, it would be obvious to use the magnetite particles of Kobiyashi et al as the carrier in the ice nucleation construct of Mie et al, as Kobiyashi et al teaches that the carrier also has strong ice nucleating abilities, which will presumably make a more effective ice nucleating agent. As Mie et al explicitly discusses nanoparticles as carriers, an artisan in this field would attempt this modification with a reasonable expectation of success.
Furthermore, it would be obvious to use the method of Feng et al to attach the polypeptide of Mie et al to the surface of the particles, as a substitution of one known element (the methods of Mie et al) for another (the method of Feng et al) yielding expected results (attachment of the polypeptide to the surface). As Mie et al is very general in how to attach the polypeptides, and mentions using glutaraldehyde and a silane, similar to the approach of Feng et al, an artisan in this field would attempt this attachment method with a reasonable expectation of success.
Kobiyashi et al discuss a metal oxide particle. Mie et al render obvious attaching ice nucleating proteins to the particle. Feng et al render obvious using APTES and glutaraldehyde to attach the particle. Thus, the combination renders obvious claims 1, 3, and 4.
Kobiyashi et al uses a magnetite particle, an iron oxide, rendering obvious claims 2 and 11.
Feng et al discusses mixing magnetite (iron oxide) particles in the nanometer size range with a solvent, immobilizing an amino organosilane to the substrate, reacting a dialdehyde to the aminosilane, then immobilizing the protein, rendering obvious claim 5.
Both Mie et al and Kobiyashi et al discuss using their materials to nucleate ice, which requires application to water. Thus, the combination of references renders obvious claim 8.
Claim 9 describes an intended use; so long as the material is appropriate for the use, the limitations are met. There is nothing in the construct of Mie et al, Kobiyashi et al, and Feng et al that would render it unsuitable for such a purpose, rendering this claim obvious.
response to applicant’s arguments
Applicants have pointed to differences between the individual references cited and their invention, that the teachings are non-analogous (freezing promotion vs. supercooling properties), that none of the references discuss the sequential linkage of the claims, and claim synergy, an alleged unexpected result.
Applicant's arguments filed 16 Jan, 2026 have been fully considered but they are not persuasive.
Applicants have pointed to the differences between each cited reference and the examined claims. However, the rejection is not based on any one of the cited references, but the combination of the references.
Applicants argue that Mie et al teaches nucleation, while Kobiyashi et al discusses supercooling. Applicants should re-read Kobiyashi et al; as noted in the rejection, the reference teaches that iron oxide nucleates ice formation.
Applicants argue that none of the references teach the sequential linkage claimed by applicants. That is not correct; Feng et al teaches how to attach a protein to an iron oxide particle, using the exact same sequential linkages. Note that coating a particle with amidated silicon oxide using APTES, reacting it with a bifunctional linker, and reacting the linker with a desired coating is common in the art.
Finally, applicants argue synergy, an alleged unexpected result. It is applicant’s responsibility to demonstrate that results are unexpected (MPEP 716.02(b)(I)) and to explain any data presented (MPEP 716.02(II)). This has not been done. Nowhere does the disclosure mention synergy, nor is it clearly obvious from the data presented.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658