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 .
Status of claims
Claims 17, 21-25 and 28-33 as amended and new claim 34 as filed on 5/18/2026 are currently pending.
Claims 21-23, 30 and 32 were withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to non-elected inventions.
Claims 17, 24, 25, 28, 29 and 33 as amended and new claim 34 as filed on 5/18/2026 are under examination in the instant office action.
Notes:
Please, notes that last listing of claims and remarks (5/18/2026) indicates that claims and remarks belong to 17/292,971 not the instant case.
Claim Objections
Claim 34 is objected to because of the following informalities:
Claim 34 as written does not have a coma at the end. Appropriate correction is required.
Claim Rejections - 35 USC § 112
Indefinite
Claims 33 and 34 (as amended and new) are 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.
Claims 33 and 34 recite respectively the use of a N-terminal nucleated form of the INP of Pseudomonas syringae and the use of INP of Pseudomonas syringae lacking a transport sequence for localization in the outer membrane. However, in view of specification these forms of INP provide for INP localization in cytoplasm and inner membrane (see par. 0035 and 0038 of published application US 202//-348614). But preceding claim 17 limited to INP being solely anchored at an outer membrane. Thus, there is insufficient antecedent basis for these limitations in the claims.
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.
Claims 17, 24, 25, 28, 29 and 33 as amended and new claim 34 remain/are rejected under 35 U.S.C. 103 as being unpatentable over Kassmannhuber et al (“Functional display of ice nucleation protein InaZ on the surface of bacterial ghosts”. BIOENGINEERED, 2017, Vol. 8, No. 5, pages 488-500) in view of EP 1 829 890 (Yasuhiro)(IDS reference), and WO 2018/201161 (Shakeel et al).
The cited reference by Kassmannhuber (2017) discloses a bacterial preparation comprising inactivated bacterial ghosts (BGs) or fragments derived from recombinant E.coli that are carrying or comprising heterologous ice nucleation protein (INP) from Pseudomonas syringae, wherein INP is anchored or displayed on the outer membrane and wherein INP is InaZ protein (see abstract).
The cited reference by Kassmannhuber does not teach that the bacterial ghosts and/or fragments carrying INPs are fixed with a fixation agent.
However, the prior art teaches, for example: EP 1 829 890 (Yasuhiro), teaches that polypeptides INP including INP derived from Pseudomonas syringae are difficult to be used in a pure form as materials for promoting freezing of water (par. 0006, 0008) and that the polypeptides are treated with cross-linking agents such as glutaraldehyde (0073).
The cited document WO 2018/201161 (Shakeel et al) clearly acknowledges that fixative agents including glutaraldehyde provide stability for cell-based preparations (0014), wherein the cell-based preparations comprise anucleated cells produced from bacteria including E.coli (par. 0009, pages 2-3) carrying heterologous polypeptide (page 4, last line) such as ice nucleation protein (page 5, line 7).
Therefore, it would have been obvious to one having ordinary skill in the art at the time the claimed invention was made to modify the bacterial preparations carrying INPs disclosed by Kassmannhuber by treatment with a fixation agent or glutaraldehyde with a reasonable expectation of success in providing stable and beneficial preparations because prior art teaches and suggests that polypeptides INP including INP derived from Pseudomonas syringae are difficult to be used in a pure form as materials for promoting freezing of water, that the polypeptides displayed on surface of delivery carriers should be treated with cross-linking agent or glutaraldehyde (EP 1 829 890) and that fixative agents including glutaraldehyde provide stability for cell-based preparations comprising cellular material including E.coli carrying heterologous polypeptide including INPs (WO 2018/201161).
Thus, the claimed invention as a whole was clearly prima facie obvious, especially in the absence of evidence to the contrary.
The claimed subject matter fails to patentably distinguish over the state art as represented be the cited references. Therefore, the claims are properly rejected under 35 USC § 103.
Response to Arguments
Applicant's arguments filed on 5/18/2026 have been fully considered but they are not all found persuasive.
With regard to claim rejection under 35 U.S.C. 103 Applicants argued the secondary references (EP 1 829 890 (Yasuhiro) and WO 2018/201161 (Shakeel et al)) do not suggest fixation of INP on bacterial ghosts and that glutaraldehyde treatment of ghosts of bacterial cells carrying ice nucleation protein as shown in the present application (example 7 and figure 5) unexpectedly provided for formation of ice crystals at relatively high temperatures of -3.81°C.
In particular, Applicants argue that Yasuhiro teaches glutaraldehyde treatment of anti-freeze proteins but not INP which are proteins different from anti-freeze proteins with regard to their amino acids sequences as recognized by Yasuhiro (0007). This argument is not found persuasive because the teaching/suggestion of Yasuhiro is drawn to polypeptide immobilization and glutaraldehyde stabilization of polypeptides on a surface of the carrier so that the polypeptide sites for binding to water and/or ice crystals are exposed outside of the carrier, facilitating their contact with water or hydrous substance (0076). Thus, although amino sequences of INP and antifreeze proteins are/might be different, the cited reference clearly points out to one of skill in the art that cross-linking with glutaraldehyde provides for stabilization of surface structures responsible binding to water, aggregation of water molecules and formation of ice crystals.
In particular, Applicants argue that teaching/suggestion of glutaraldehyde treatment by cited document WO 2018/201161 (Shakeel et al) is directed to “anucleated” cells as delivery vehicle of beneficial polypeptide but not bacterial cell ghosts as delivery vehicles of INP. This argument is not found persuasive for the main reason that the cited document WO 2018/201161 (Shakeel et al) clearly acknowledges that fixative agents including glutaraldehyde provide stability for cell-based preparations (0014), wherein the cell-based preparations are delivery vehicles of heterologous polypeptide (page 4, last line) including ice nucleation protein (page 5, line 7). Further, although anucleated cells (or “minicells”) might or might not contain cytoplasm materials, they are not living and non-propagating cells (par. 0081) as the bacterial cell ghosts of the claims are not living. Thus, whether anucleated cell-based delivery vehicle or a bacterial cell ghost-based delivery vehicle of the same polypeptides, they are both no longer represent living/propagating genetically modified organisms. Therefore, one of skill in the art would reasonably and obviously consider to treat non-living cell-based delivery vehicles with the same cross-linking agent as intended for stabilization of heterologous polypeptides.
With respect to unexpected showing as argued by Applicants it is noted that any combination for which unexpected effect is not clearly established would be properly rejected because non-obviousness would not have been established.
In the insntst case, the as-filed specification (example 7 and figure 5) demonstrate formation of ice crystals at temperatures of -3.81°C for bacterial ghosts carrying INP (InaZ-cyto and InaZ-OM) that were treated with glutaraldehyde but comparative data for untreated bacterial ghosts carrying INP produced under the same experimental protocol design is not shown.
Applicants argue that prior art untreated bacterial ghosts carrying INP of cited refence by Kassmannhuber demonstrate formation of ice crystals at lower temperatures of -5.6-6.7°C. However, the conditions of the experiments disclosed by the cited refence might be different and, thus, cannot be relied for a proper establishment of unexpected effects/results.
It is well recognized that unexpected effects are highly unpredictable results that are very dependent on the specific conditions used in the particular experiments. Thus, any combination for which unexpected effect is not clearly established would be properly rejected because non-obviousness would not have been established.
No claims are allowed.
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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Vera Afremova
August 3, 2026
/VERA AFREMOVA/ Primary Examiner, Art Unit 1653
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