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.
Applicant's response, filed on 03/24/2026, has been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Status of claims
Claims 1-2, 4-5, 7-14, 16, 21, 23, 40, 42-43, and 47-55 are pending.
Claims 3, 6, 15, 17-20, 22, 24-39, 41 and 44-46 are canceled.
Claim 1 is amended.
Claims 9-14, 16, 21, 23, 40, 42-43 and 50-55 are withdrawn.
Claims 1-2, 4-5, 7-8 and 47-49 are examined on the merits.
Priority
The present application was filed as a proper National Stage (371) entry of PCT Application No. PCT/CN2020/077472, filed 03/02/2020. Acknowledgment is also made of applicant's claim for foreign priority under 35 U.S.C. 119(a)-(d) to Application No. CN201910282416.X, CN201910281986.7, CN201910282417.4, CN201910282418.9 and CN201910282422.5, filed on 04/09/2019 in China.
Information Disclosure Statement
The Information Disclosure Statement filed on 12/24/2025 is in compliance with the provisions of 37 CFR 1.97 and have been considered in full. A signed copy of the list of references cited from each IDS is included with this Office Action.
Withdrawn Rejections/Objections
The rejection of claims 1-2, 4-5, 7-8 and 47-49 under 35 U.S.C. §112(b), Second Paragraph, in the Office action mailed 12/31/2025 is withdrawn in view of the amendments filed 03/24/2026.
Regarding 35 USC 101
Claims 1-2, 4-5, 7-8 and 47-49 are patent-eligible under 35 U.S.C. 101 because independent claim 1 recites “Step 3: selecting one or more compound molecules having or exceeding a predetermined affinity for ice and a predetermined affinity for water from the plurality of compound molecules, wherein the spreading performance correlates to the affinity and Step 4: synthesizing the selected one or more compound molecules from Step 3 to obtain the ice growth inhibition material,” which integrates the judicial exceptions into a practical application under Step 2A, 2nd prong of the 101 analysis.
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.
Claims 1-2, 4-5, 8 and 47-48 are rejected under 35 U.S.C. 103 as being unpatentable over Weng ("Molecular dynamics at the interface between ice and poly (vinyl alcohol) and ice recrystallization inhibition." Langmuir 34.17 (2017): 5116-5123; cited on the 01/06/2025 “Notice of References Cited” form 892), in view of Hedir (“Synthesis of degradable poly (vinyl alcohol) by radical ring-opening copolymerization and ice recrystallization inhibition activity.” ACS macro letters 6.12 (2017): 1404-1408.; cited on the 06/17/2025 “Notice of References Cited” form 892.) and Wu ("Cooperative behavior of poly (vinyl alcohol) and water as revealed by molecular dynamics simulations." Polymer 51.19 (2010): 4452-4460.; cited on the attached “Notice of References Cited” form 892.). Any newly recited portions herein are necessitated by claim amendment.
Regarding claim 1, Weng teaches A molecular design method for an ice growth inhibition material. Weng teaches "The findings in this study will help pave the path for addressing a pressing challenge in designing synthetic ice recrystallization inhibitors rationally, by enriching our mechanistic understanding of IRI process by macromolecules." (abstract).
Weng teaches the recited Step 1: constructing a library for a plurality of compound molecules, wherein each of the plurality of compound molecules comprises a hydrophilic group and an ice-philic group, wherein the hydrophilic group and the ice-philic group are different or the same. Weng teaches "Three lengths of poly(vinyl alcohol) PVA were investigated in this study, namely, n = 5, 10, and 20, as shown in Scheme 1." (Page 117, col. 2, para. 2). The different lengths of PVA taught by Weng corresponds to the recited library for structures of compound molecules. Scheme 1 depicts the PVA with hydroxyl groups, which is the hydrophilic group and the ice-philic group as defined by the specification. According to the specification the hydrophilic group (page 2, last paragraph of the instant application) and the ice-philic group (page 3, para. 1 of the instant application) maybe a hydroxyl (-OH) group. Therefore, the hydroxyl groups of PVAs in scheme 1 taught by Weng corresponds to the recited structures of compound molecules with hydrophilic group and ice-philic group.
Weng teaches the recited Step 2: simulating and evaluating a spreading performance of each of the plurality of compound molecules at an ice-water interface by calculating interactions between the compound molecules, interactions between the compound molecules and water molecules, and interactions between the compound molecules and ice-water molecules using a method for molecular dynamics (MD) simulation. Weng teaches "Our molecular dynamics simulations revealed a stereoscopic, geometrical match between the hydroxyl groups of PVA and the water molecules of ice, and provided microscopic evidence of the adsorption of PVA to both the basal and prism faces of ice and the incorporation of short-chain PVA into the ice lattice. The length of PVA, i.e., the number of hydroxyl groups, seems to be a key factor dictating the performance of IRI, as the PVA molecule must be large enough to prevent the joining together of adjacent curvatures in the ice front."(Abstract) and "During the simulation, the ice crystal grew layer by layer. Figure 1 displays representative snapshots of the ice−water systems in the absence or presence of PVA at t = 10, 30, and 60 ns, respectively. At t = 10 ns, ice crystals had grown two additional layers from each side of the seed ice. Meanwhile, PVA, regardless of the chain length, began to adsorb onto the frontier ice layers. Pronounced interruption against the frontier ice layers by PVA was observed at t = 30 ns, showing evident structural defects. As the simulations were run for another 30 ns, however, the ice layers engulfed PVA5 and PVA10 into the ice crystal lattice. In contrast, the structural defect attributed to PVA20 persisted and expanded during the 60 ns period. As a result, the ice layers only accumulated on the sides in the PVA20−ice−water system. " (Page 5118, Col. 2, Para. 3). Spreading performance is interpreted to mean the interaction of the compound molecule with ice or water. Figure 1 depicts the spreading performance of PVA as time progresses from 10ns to 30ns and to 60ns.
Weng teaches the recited calculating interactions between the compound molecules and the water molecules, and interactions between the compound molecules and ice-water molecules with Figure 7, Hydrogen-bonding characterization. Fig. 7 depicts the number of hydrogen bonds formed between PVA (the one below the seed ice) and TIP4P/2005 (either water or ice). (A: PVA5; B: PVA10; C: PVA20) The number of hydrogen bonds formed between ice molecules (D). Gray bars: −OH group of PVA as the H acceptor; black bars: −OH group of PVA as the H donor. The recited calculating interactions corresponds to the number of hydrogen bonds formed as taught by Weng. It is noted that the recited “water molecules” correspond to H2O in the liquid and/or the solid states.
Weng teaches the recited wherein the calculation involves one or more parameters selected
from: 1) contactable surf ace areas of the plurality of compound molecules with water molecules
and ice-water molecules at an ice-water interface, 2) aggregation probabilities of the plurality of
compound molecules in an aqueous solution, and 3) number of the intermolecular hydrogen
bonds formed between the plurality of compound molecules and water in an aqueous solution,
and number of the intermolecular hydrogen bonds formed between the plurality of compound
molecules and water molecules and ice-water molecules at an ice-water interface with “The hydrogen-bonding characterization is shown in Figure 7. As seen in Figure 7A-C, each hydroxyl oxygen atom of a PVA molecule is able to donate its bonded hydrogen atom to a surrounding water/ice molecule to form one hydrogen bond, while as a H-acceptor, it can form 1 or 2 hydrogen bond(s) with its surrounding water/ice molecule(s). In a stable ice lattice, each ice molecule typically forms two hydrogen bonds as H-donor and two hydrogen bonds as H-acceptor (Figure 7D). Moreover, we suggest that the hydroxyl oxygen atom of PVA will form about three hydrogen bonds with the surrounding ice molecules (i.e., NHBond≈3) when it fits into the ice lattice perfectly. Figure 7A shows that both O9 and O11 of PVA5 have about three hydrogen bonds with the surrounding ice molecules. Their corresponding g(r)s show a primary peak around 2.75 Å, a minimum around 3.5 Å and a second primary peak around 4.5 Å (Figure 5C), demonstrating the essential features of an ice lattice. However, a moderate match between OOH and Oice (e.g., O3 and O7) or a complete mismatch (e.g., O5) will contribute to NHBond≤2. The validity of NHBond being an indicator for the fit of OOH into the ice lattice was also confirmed for PVA20 on O3 and O5 which were found to perfectly fit into the ice lattice, and O35 which was highly mobile and exposed to the liquid phase (See Figure 7C and Figure S4 in SI). (page 5120, col. 2, para. 3) and with “The hydrogen bonds in the (PVA-)ice-water systems were determined via the geometrical criteria. A certain aggregate between two oxygen atoms is identified as a hydrogen bond if the O⋯O distance does not exceed 3.5 Å and the angle O–H⋯O is greater than 145°.” (page 5118, col. 2, para. 2). Weng teaches the number of the intermolecular hydrogen bonds formed between PVA and water/ice molecule.
However, Weng does not explicitly teach calculating interactions between the compound molecules. This limitation is taught by Wu as discussed below.
Weng teaches the recited Step 3: selecting one or more compound molecules having or exceeding a predetermined affinity for ice and a predetermined affinity for water from the plurality of compound molecules, wherein the spreading performance correlates to the affinity. Weng teaches "The result presented in Figure S2 B demonstrates that the ice-binding activity of PVA20 is also independent of the polymer tacticity as curvatures had emerged upon the adsorption of PVA 20 onto the ice front by t =40 ns." (Page 5119, Col. 1, Para. 2). Weng also teaches "As seen in Figure 2, the PVA20−ice− water system constantly had fewer ice molecules than the other three systems (i.e., ice−water, PVA5−ice−water and PVA10− ice−water)" (Page 5119, col. 1, para. 3 to page 5119, col. 2, para. 1). Figure 2 shows that PVA20 had fewer ice molecules when compared to the other PVAs. It is interpreted that desired affinities corresponds to the PVA20 ice− water system that constantly had fewer ice molecules when compared to the other three systems.
Weng teaches "The hydrogen-bonding characterization is shown in Figure 7. As seen in Figure 7A−C, each hydroxyl oxygen atom of a PVA molecule is able to donate its bonded hydrogen atom to a surrounding water/ice molecule to form one hydrogen bond, while as a H-acceptor, it can form 1 or 2 hydrogen bond(s)with its surrounding water/ice molecule(s). In a stable ice lattice, each ice molecule typically forms two hydrogen bonds as H-donor and two hydrogen bonds as H-acceptor (Figure7D). Moreover, we suggest that the hydroxyl oxygen atom of PVA will form about three hydrogen bonds with the surrounding ice molecules (i.e., NHBond ≈ 3) when it fits into the ice lattice perfectly. Figure 7A shows that both O9 and O11 of PVA 5 have about three hydrogen bonds with the surrounding ice molecules. (page 5120, col 2, para. 3) Their corresponding g(r)s show a primary peak around 2.75 Å, a minimum around 3.5 Å and a second primary peak around 4.5 Å (Figure 5C), demonstrating the essential features of an ice lattice. However, a moderate match between OOH and Oice (e.g., O3 and O7) or a complete mismatch (e.g., O5) will contribute to NHBond ≤ 2. The validity of NHBond being an indicator for the fit of OOH into the ice lattice was also confirmed for PVA 20 on O3 and O5 which were found to perfectly fit into the ice lattice, and O35 which was highly mobile and exposed to the liquid phase (see Figure 7C and Figure S4 in SI) (page 5121, col 1, para. 1)." The recited affinity for ice and affinity for water corresponds to the number of hydrogen bond formed between PVA and with its surrounding water/ice molecule(s) as taught by Weng.
Weng teaches Step 4: the interactions are selected from formation of a hydrogen bond, a Van der Waals interaction, an electrostatic interaction, a hydrophobic interaction, and a π-π interaction with "The hydrogen bonds in the (PVA−)ice−water systems were determined via the geometrical criteria. 40 A certain aggregate between two oxygen atoms is identified as a hydrogen bond if the O···O distance does not exceed 3.5 Å and the angle O−H···O is greater than 145°." (page 3118, col. 2, para. 2) and "The simulations in this study were conducted by using the MD simulation package NAMD. 31 The distance beyond which electrostatic and van der Waals interactions are truncated is 10Å. When the distance is beyond 8 Å, the switching functions begin to take effect to smoothly reduce electrostatic and vander Waals interactions to zero." (page 3118, col. 1, para. 1). Weng also teaches Figure 7, Hydrogen-bonding characterization. Fig. 7 depicts the number of hydrogen bonds formed between PVA (the one below the seed ice) and TIP4P/2005 (either water or ice). (A: PVA5; B: PVA10; C: PVA20) The number of hydrogen bonds formed between ice molecules (D). Gray bars: −OH group of PVA as the H acceptor; black bars: −OH group of PVA as the H donor.
Weng teaches the recited Step 4: wherein the hydrophilic group is a functional group capable of forming a non-covalent interaction with a water molecule, for example, forming a hydrogen bond, a Van der Waals interaction, an electrostatic interaction, a hydrophobic interaction or a π-π interaction with water; for example, the hydrophilic group may be selected from at least one of hydroxyl (-OH), amino (-N112), carboxyl (-COGH) and amido (-CONII2), or, for example, from a compound molecule, such as a hydrophilic amino acid such as proline (L-Pro), arginine (L-Arg) and lysine (L-Lys), glucono delta-lactone (GDL) and a saccharide, and a molecular fragment thereof. Weng teaches "Our molecular dynamics simulations revealed a stereoscopic, geometrical match between the hydroxyl groups of PVA and the water molecules of ice, and provided microscopic evidence of the adsorption of PVA to both the basal and prism faces of ice and the incorporation of short chain PVA into the ice lattice" (Abstract) and "As seen in Figure 7A−C, each hydroxyl oxygen atom of a PVA molecule is able to donate its bonded hydrogen atom to a surrounding water/ice molecule to form one hydrogen bond, while as a H-acceptor, it can form 1 or 2 hydrogen bond(s) with its surrounding water/ice molecule(s). In a stable ice lattice, each ice molecule typically forms two hydrogen bonds as H-donor and two hydrogen bonds as H-acceptor (Figure 7D). Moreover, we suggest that the hydroxyl oxygen atom of PVA will form about three hydrogen bonds with the surrounding ice molecules (i.e., NHBond ≈ 3) when it fits into the ice lattice perfectly." (Page 5119, col. 2, para. 3).
Weng teaches the recited the hydrophilic group is selected from hydroxyl (-OH), amino (-NH2), phenyl (-C6H5), pyrrolidinyl (-C4H8N) and the like, or, for example, from a compound molecule, such as an ice-philic amino acid such as glutamine (L-Gln), threonine (L-Thr) and aspartic acid (L-Asn), a benzene ring (C6H6) and pyrrolidine (C4H9N). Weng teaches "Our molecular dynamics simulations revealed a stereoscopic, geometrical match between the hydroxyl groups of PVA and the water molecules of ice, and provided microscopic evidence of the adsorption of PVA to both the basal and prism faces of ice and the incorporation of short chain PVA into the ice lattice" (Abstract) and "As seen in Figure 7A−C, each hydroxyl oxygen atom of a PVA molecule is able to donate its bonded hydrogen atom to a surrounding water/ice molecule to form one hydrogen bond, while as a H-acceptor, it can form 1 or 2 hydrogen bond(s) with its surrounding water/ice molecule(s). In a stable ice lattice, each ice molecule typically forms two hydrogen bonds as H-donor and two hydrogen bonds as H-acceptor (Figure 7D). Moreover, we suggest that the hydroxyl oxygen atom of PVA will form about three hydrogen bonds with the surrounding ice molecules (i.e., NHBond ≈ 3) when it fits into the ice lattice perfectly." (Page 5119, col. 2, para. 3).
The multiple hydroxyl groups of PVA (see for example Figure 6, there are multiple hydroxyl groups) taught by Weng corresponds to the recited hydrophilic group and ice-philic group.
Weng does not teach synthesizing the compound molecules of claim 1, Step 4. However, this limitation is taught by Hedir.
Weng does not explicitly teach calculating interactions between the compound molecules of claim 1, Step 1. However, this limitation is taught by Wu.
The teachings of Hedir are involved in the synthesis of degradable PVA with ice recrystallization inhibition and analysis of PVA ice inhibition which is similar to the teachings of Weng.
Hedir teaches the claim limitation of synthesizing is by polymerization with “…our the aim was to synthesize degradable, ester-containing poly(vinyl alcohol) but with full retention of its potent IRI activity. We demonstrate a radical ring-opening polymerization strategy and that IRI activity can be retained if the MDO incorporation is controlled to achieve a balance between degradability and function. (Page 1405, col. 1, para. 2).
As discussed above, Weng teaches the recited calculating interactions between the compound molecules and the water molecules, and interactions between the compound molecules and ice-water molecules with Figure 7, Hydrogen-bonding characterization. Fig. 7 depicts the number of hydrogen bonds formed between PVA (the one below the seed ice) and TIP4P/2005 (either water or ice). (A: PVA5; B: PVA10; C: PVA20) The number of hydrogen bonds formed between ice molecules (D). Gray bars: −OH group of PVA as the H acceptor; black bars: −OH group of PVA as the H donor. The recited calculating interactions corresponds to the number of hydrogen bonds formed as taught by Weng. It is noted that the recited “water molecules” correspond to H2O in the liquid and/or the solid states.
However, Weng does not explicitly teach calculating interactions between the compound molecules. This limitation is taught by Wu. Wu also teaches the claim limitation of interactions between the compound molecules and the water molecules and interactions between the compound molecules and ice-water molecules as discussed below.
Wu teaches the claim limitation of calculating interactions between the compound molecules, interactions between the compound molecules and the water molecules, and interactions between the compound molecules and ice-water molecules with “The simulated activation energy at lower temperatures is lower by 4.17 kcal/mol than that at higher temperatures, which is on the order of the energy for hydrogen bonding between PVA and H2O, that is, 4.71e5.15 kcal/mol.” (page 4457, col. 1, para. 3), “The total HB number per hydroxyl group is plotted as function of temperature, as shown in Fig. 7(a). It can be seen that this value at each temperature is just a bit bigger than the coordination number of water molecules to oxygen atoms of PVA, which indicates that besides between hydroxyl groups and water molecules HBs also form between hydroxyl groups on PVA and between H2O and H2O. Furthermore, this value monotonously decreases with increasing temperature, which almost approaches straight line at both temperature regions. An abrupt change in the slope of the straight lines can be obviously seen, which marks the occurrence of glass transition as for the specific volume and diffusion coefficient. This phenomenon confirms that HB interactions in the whole system play a key role in glass transition. When the same analysis procedure is carried out separately on the three pairs, PVA-PVA, PVA-H2O, and H2O-H2O, no similar phenomenon turns up as shown in Fig. 7(b), which suggests that the properties of the whole system (such as Tg) depend on not only the HB interactions between PVA and H2O (PVA-H2O) but also on those between PVA and PVA (PVA-PVA) and those between H2O and H2O (H2O-H2O).” (page 4459, col. 1, para. 2) and Figure 7 (page 4456). Fig. 7 depicts Total HB number (a) and HB number between pairs (b) per hydroxyl group in the PVAeH2O system as function of temperature. Section 3.3.1 Radial distribution functions (page 4457, col. 2) of Wu also discusses the formulas used to calculate RDF that provides a first insight into the Hydrogen Bonds interactions. The recited “interactions between the compound molecules” and “interactions between the compound molecules and the water molecules” corresponds to HB interactions between PVA and H2O (PVA-H2O) and those between PVA and PVA (PVA-PVA) as taught by Wu.
It would have been prima facia obvious to one having ordinary skill to combine the teachings of Weng and Hedir. Hedir showed that their method of the synthesis degradable PVA was able to inhibit ice before and after degradation (Fig. 4, page 1406). Hedir’s synthesized PVA increases the number of recovered viable cells due to its potent ice recrystallization inhibition when added to cellular cryopreservation solutions (Abstract). A person of ordinary skill in the art would have been motivated to modify the method of Weng to include synthesizing PVAs as taught by Hedir because of the synthesized PVA’s potent ice recrystallization inhibition ability. Furthermore, there would have been a reasonable expectation of success because based on Hedir, it was known to synthesize PVA with improved ice inhibition properties, and since Weng is teaching screening for PVAs with improved ice inhibition, one would therefore expect success applying the known synthesis technique to therefore produce the selected compounds.
It would have also been prima facia obvious to one having ordinary skill to combine the teachings of Weng and Wu to include calculating interactions between the compound molecules of PVA to better elucidate the structure and properties of the polymers and water system (page 4452, col. 2, para. 2). Furthermore, there would have been a reasonable expectation of success because both Weng and Wu teach methods that analyze PVA and its interaction with water.
Regarding claim 2, Weng teaches the recited wherein the MD simulation of the step (2) is performed by GROMACS, AMBER, CHARMM, NAMD, or LAMMPS. Weng teaches "The simulations in this study were conducted by using the MD simulation package NAMD" (Page 5118, Col. 1, Para. 2).
Regarding claim 4, Weng teaches the recited a temperature and a pressure are adjusted when performing the MD simulation on the interactions between the molecules. Wang teaches "Each simulation was run for 100 ns with an isothermal−isobaric (NpT) ensemble in which the temperature and pressure were fixed at 230 K and 101.325 kPa, respectively. The simulation temperature is about 22 K below the melting point of TIP4P/2005 (i.e., 252.1 K)." (page 5118, col. 1, para. 1). The fixing of temperature and pressure of Weng corresponds to the recited adjusting temperature and pressure. See at claim 4, the claim as recited only clearly requires “the MD simulation of the step (2), a temperature and pressure are adjusted when the simulation and calculation are performed on the interactions between the molecules”, the limitations following “preferably” are not clearly recited as limiting with respect to the recited claim (see above, addressed under 35 U.S.C. 112(b)).
Regarding claim 5, Weng teaches the recited wherein a main chain of each of the plurality of compound molecules is a carbon chain or peptide chain structure. Weng teaches Scheme 1. Chemical Structure of Poly(vinyl alcohol) (Top Right) And the Backbone Chain of PVA5 (n = 5), PVA10 (n = 10), and PVA20 (n = 20) (Bottom)a (page 5117). Scheme 1 depicts Poly(vinyl alcohol) with carbon chain.
Regarding claim 8, Weng teaches the effects of different lengths of PVA on ice formation, but does not explicitly teach wherein in Step 4, the synthesizing is by polymerization, dehydration condensation, or biological fermentation of genetically engineered bacteria. However, this limitation is taught by Hedir.
The teachings of Hedir are involved in the synthesis of degradable PVA with ice recrystallization inhibition and analysis of PVA ice inhibition which is similar to the teachings of Weng.
Hedir teaches the claim limitation of synthesizing is by polymerization with “…our the aim was to synthesize degradable, ester-containing poly(vinyl alcohol) but with full retention of its potent IRI activity. We demonstrate a radical ring-opening polymerization strategy and that IRI activity can be retained if the MDO incorporation is controlled to achieve a balance between degradability and function. (Page 1405, col. 1, para. 2).
It would have been prima facia obvious to one having ordinary skill to combine the teachings of Weng and Hedir. Hedir showed that their method of the synthesis degradable PVA was able to inhibit ice before and after degradation (Fig. 4, page 1406). Hedir’s synthesized PVA increases the number of recovered viable cells due to its potent ice recrystallization inhibition when added to cellular cryopreservation solutions (Abstract). A person of ordinary skill in the art would have been motivated to modify the method of Weng to include synthesizing PVAs by polymerization as taught by Hedir because of the synthesized PVA’s potent ice recrystallization inhibition ability. Furthermore, there would have been a reasonable expectation of success because based on Hedir, it was known to synthesize PVA with improved ice inhibition properties, and since Weng is teaching screening for PVAs with improved ice inhibition, one would therefore expect success applying the known synthesis technique to therefore produce the selected compounds.
Regarding claim 47, Weng teaches the recited wherein the MD simulation of the step 2, a model of a water molecule is selected from models of TIP3P, TIN4P, TIP4P/2005, SPC, TIP3P, TIP5P and SPC/E, preferably TJP4P/2005 model of a water molecule. Weng teaches "In each simulation box, a single layer of hexagonal ice, containing 1280 TIP4P/2005 molecules, was fixed in the x−z plane, serving as the seed ice (Scheme 2)" (Page 5117, Col. 2, Para. 2).
Weng teaches the recited a force field parameter is provided by one of GROMOSTM, ESFF (Extensible Systematic Force Field), MM force field (Molecular Mechanics force field), AMBERTM, CHARMMTM, COMPASSTM (Condensedphase Optimized Molecular Potentials for Atomistic Simulation Studies), UFF (Universal Force Field), CVFF (Consistent Valence Force Field), and other force fields. Weng teaches "The force field parameters for PVA were generated through MATCH" (Page 5118, Col. 1, Para. 1).
Regarding claim 48, Weng teaches the recited a temperature and a pressure are adjusted when performing the MD simulation on the interactions between the molecules. Wang teaches "Each simulation was run for 100 ns with an isothermal−isobaric (NpT) ensemble in which the temperature and pressure were fixed at 230 K and 101.325 kPa, respectively. The simulation temperature is about 22 K below the melting point of TIP4P/2005 (i.e., 252.1 K)." (page 5118, col. 1, para. 1). The fixing of temperature and pressure of Weng corresponds to the recited adjusting temperature and pressure. See at claim 4, the claim as recited only clearly requires “the MD simulation of the step (2), a temperature and pressure are adjusted when the simulation and calculation are performed on the interactions between the molecules”, the limitations following “preferably” are not clearly recited as limiting with respect to the recited claim (see above, addressed under 35 U.S.C. 112(b)).
Weng teaches the recited periodic boundary conditions are adopted for x-direction, y-direction and z-direction when an aqueous solution system is simulated; periodic boundary conditions are adopted for x-direction, y-direction and z-direction when an aqueous system is simulated. Weng teaches "Periodic boundary conditions were applied and the Particle Mesh Ewald (PME) method was employed, such that the configuration of the seed ice was periodically replicated in the x−z plane" (page 5118, col. 1, para. 2). The x−z plane of Weng correspond to the recited x-direction, y-direction and z-direction.
Weng also teaches "Figure 1. Snapshots of the (PVA−)ice−water systems viewed in the x−y plane at t = 10, 30, and 60 ns as the ice crystal grew at 230 K" (page 5118). The x−y plane of Weng corresponds to the recited x-direction and y-direction.
Weng teaches the recited a cubic or octahedral box of water is selected. Weng teaches "In this study, the PVA molecules that were initially placed in the water box for pre-equilibration at 300 K were isotactic." (page 5119, col. 1, para. 2). The water box of Weng corresponds to the recited cubic box of water.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Weng (Molecular dynamics at the interface between ice and poly (vinyl alcohol) and ice recrystallization inhibition." Langmuir 34.17 (2017): 5116-5123; cited on the 01/06/2025 “Notice of References Cited” form 892), in view of Hedir (“Synthesis of degradable poly (vinyl alcohol) by radical ring-opening copolymerization and ice recrystallization inhibition activity.” ACS macro letters 6.12 (2017): 1404-1408.; cited on the 06/17/2025 “Notice of References Cited” form 892) and Wu ("Cooperative behavior of poly (vinyl alcohol) and water as revealed by molecular dynamics simulations." Polymer 51.19 (2010): 4452-4460.; cited on the attached “Notice of References Cited” form 892.) as applied to claims 1-2, 4-5, 8 and 47-48 above and Mastai ("Control over the structure of ice and water by block copolymer additives." ChemPhysChem 3.1 (2002): 119-123.; cited on the 01/06/2025 “Notice of References Cited” form 892).
Weng, Hedir and Wu are applied to claims 1-2, 4-5, 8 and 47-48 as discussed above.
Regarding claim 7, Weng teaches "Therefore, a number of synthetic substitutes have been discovered or developed, such as poly(vinyl alcohol) PVA, double hydrophilic block copolymers, zirconium acetate, D-glucose derivatives bearing β-linked para-methoxyphenyl, graphene oxide, and self-assembled, amphipathic metallohelicies." (Page 5117, col. 1, para. 1).
Although Weng mentions double hydrophilic block copolymers, Weng does not explicitly teach wherein the ice growth inhibition material is formed by covalently bonding a block comprising a hydrophilic group to a block comprising the ice-philic group, or is formed by ionically bonding a molecule comprising the hydrophilic group to a molecule comprising the ice-philic group of claim 7. However, this limitation is taught by Mastai.
Mastai teaches the formation of double hydrophilic block copolymers. Masti teaches "Recently, we introduced a novel class of synthetic macro-molecules which step very efficiently into crystallization events, namely the double hydrophilic block copolymers (DHBCs). [4] Those molecules consist of one block or functionality pattern, which strongly interacts with organic/inorganic crystal surfaces, whereas another hydrophilic part or block provides water solubility." (Page 119, col. 2, para. 4) and "The interacting part of the polymers is usually oligomeric (6 ±20 functional groups) and can be designed in a way that it fits a distinct crystal packing arrangement of a selected crystal face. Previously, we have demonstrated the facility of this concept and used designed DHBCs to control morphologies of various biominerals, including calcium carbonate, [5, 6] calcium phosphate, [7] and barium sulfate. [8] In this paper, we describe the effects of DHBCs on the nucleation and growth of ice crystals, to mimic the natural AFPs." (Page 119, col. 2, para. 5). The organic/inorganic crystal surfaces of Mastai corresponds to ice, therefore the block or functionality pattern, which strongly interacts with organic/inorganic crystal surfaces corresponds to the recited ice-philic group. The double hydrophilic block copolymers of Weng corresponds to the recited claim limitation.
It would have been prima facia obvious to one having ordinary skill before the effective filing date of the claimed invention to combine the teachings of Weng and Mastai. Mastai discusses that the double hydrophilic block copolymers can step very efficiently into crystallization events (page 119, col. 2, para. 4). A person of ordinary skill in the art would have been motivated to modify the method of Weng to form double hydrophilic block copolymers as taught by Mastai to efficiently interfere with crystallization events. Furthermore, there would have been a reasonable expectation of success because the PVA of Weng and the double hydrophilic block copolymers of Mastai are both antifreeze protein substitutes with hydrophilic side groups and can be screened using the MD simulation of Weng.
Claim 49 is rejected under 35 U.S.C. 103 as being unpatentable over Weng (Molecular dynamics at the interface between ice and poly (vinyl alcohol) and ice recrystallization inhibition." Langmuir 34.17 (2017): 5116-5123; cited on the 01/06/2025 “Notice of References Cited” form 892), in view of Hedir (“Synthesis of degradable poly (vinyl alcohol) by radical ring-opening copolymerization and ice recrystallization inhibition activity.” ACS macro letters 6.12 (2017): 1404-1408.; cited on the 06/17/2025 “Notice of References Cited” form 892) and Wu ("Cooperative behavior of poly (vinyl alcohol) and water as revealed by molecular dynamics simulations." Polymer 51.19 (2010): 4452-4460.; cited on the attached “Notice of References Cited” form 892.) as applied to claims 1-2, 4-5, 8 and 47-48 above and Emmanuel (Molecular simulation of ice growth inhibition by biomimetic antifreeze macromolecules. Diss. University of Warwick, 2015; cited on the 06/17/2025 “Notice of References Cited” form 892).
Weng, Hedir and Wu are applied to claims 1-2, 4-5, 8 and 47-48 as discussed above.
Although Weng teaches a water box that corresponds to the claim limitation cubic box of water, Weng does not teach the dimensions of the box. However, this limitation is taught by Emmanuel.
Regarding claim 49, Emmanuel teaches wherein the cubic box of water has a dimension of 3.9 X 3.6 X 1.0 nm3 with “The lengths of simulation boxes in the cited work ranged from ~3-4 nm3” (page 70, para. 1). The recited cubic box corresponds to the simulation box of Emmanuel.
It would have been prima facia obvious to one having ordinary skill before the effective filing date of the claimed invention to combine the teachings of Weng and Emmanuel. A person of ordinary skill in the art would have been motivated to modify the method of Weng to include a simulation box with the dimensions as taught by Emmanuel to better simulate conditions for the analysis of ice inhibition properties. Furthermore, there would have been a reasonable expectation of success because both Weng and Emmanuel are both analyzing PVAs and its ice inhibition properties.
Response to 35 USC §103 filed 03/24/2026 (Pages 16-20 of remarks)
Applicant’s remarks refer to amended claim 1.
Applicant argues that Weng focuses on studying interactions between PVA and ice-water molecules, and does not study on the spreading performance of PVA at an ice-water interface, which involves specific parameters, as claimed in the claimed invention.
In response, Applicant’s arguments are not persuasive. Under the BRI, as indicated in the 103 rejection above, spreading performance is broadly interpreted to refer to the interaction of the compound molecule with ice or water because this interaction determines whether ice recrystallization is inhibited. It is also noted that the specification does not clearly define the phrase, spreading performance, but states that the material with strong spreading capability has good ice growth inhibition performance (page 6, lines 29 to 31), which aligns with the interpretation. Also, step 2 in claim 1 involves calculating interactions between the compound molecules and water molecules, and interactions between the compound molecules and ice-water molecules using a method for molecular dynamics (MD) simulation that equates to the study of interactions between PVA and ice-water molecules as taught by Weng.
As discussed above in the claims 103 rejection section, Weng teaches the newly added limitation of wherein the calculation involves one or more parameters selected from: 1) contactable surface areas of the plurality of compound molecules with water molecules and ice-water molecules at an ice-water interface, 2) aggregation probabilities of the plurality of compound molecules in an aqueous solution, and 3) number of the intermolecular hydrogen bonds formed between the plurality of compound molecules and water in an aqueous solution, and number of the intermolecular hydrogen bonds formed between the plurality of compound molecules and water molecules and ice-water molecules at an ice-water interface with “The hydrogen-bonding characterization is shown in Figure 7. As seen in Figure 7A-C, each hydroxyl oxygen atom of a PVA molecule is able to donate its bonded hydrogen atom to a surrounding water/ice molecule to form one hydrogen bond, while as a H-acceptor, it can form 1 or 2 hydrogen bond(s) with its surrounding water/ice molecule(s). In a stable ice lattice, each ice molecule typically forms two hydrogen bonds as H-donor and two hydrogen bonds as H-acceptor (Figure 7D). Moreover, we suggest that the hydroxyl oxygen atom of PVA will form about three hydrogen bonds with the surrounding ice molecules (i.e., NHBond≈3) when it fits into the ice lattice perfectly. Figure 7A shows that both O9 and O11 of PVA5 have about three hydrogen bonds with the surrounding ice molecules. Their corresponding g(r)s show a primary peak around 2.75 Å, a minimum around 3.5 Å and a second primary peak around 4.5 Å (Figure 5C), demonstrating the essential features of an ice lattice. However, a moderate match between OOH and Oice (e.g., O3 and O7) or a complete mismatch (e.g., O5) will contribute to NHBond≤2. The validity of NHBond being an indicator for the fit of OOH into the ice lattice was also confirmed for PVA20 on O3 and O5 which were found to perfectly fit into the ice lattice, and O35 which was highly mobile and exposed to the liquid phase (See Figure 7C and Figure S4 in SI). (page 5120, col. 2, para. 3) and with “The hydrogen bonds in the (PVA-)ice-water systems were determined via the geometrical criteria. A certain aggregate between two oxygen atoms is identified as a hydrogen bond if the O⋯O distance does not exceed 3.5 Å and the angle O–H⋯O is greater than 145°.” (page 5118, col. 2, para. 2). Weng teaches the number of the intermolecular hydrogen bonds formed between PVA and water/ice molecule.
Conclusion
No claims are allowed.
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 KETTIP KRIANGCHAIVECH whose telephone number is (571)272-1735. The examiner can normally be reached 8:30am-5:00pm EDT.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Larry D. Riggs can be reached on (571) 270-3062. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/K.K./Examiner, Art Unit 1686
/LARRY D RIGGS II/Supervisory Patent Examiner, Art Unit 1686
Prosecution Insights