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.
Claims Status
Claims 1-13 are pending
Claims 1, 7, and 11 have been amended.
Maintained/Modified Rejections
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include "level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient" (MPEP 2163).
A claimed genus may be satisfied through sufficient description of a representative number of species or disclosure of relevant, identifying characteristics such as functional characteristics coupled with a known or disclosed correlation between function and structure(MPEP 2163(3)a(II)). The number of species that describe the genus must be adequate to describe the entire genus; if there is substantial variability, a large number of species must be described.
The analysis for adequate written description considers (a) actual reduction to practice, (b) disclosure of drawings or structural chemical formulas, (c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure and (d) representative number of samples.
The issue is if applicants have possession of antifreeze protein antibodies.
(a and b) actual reduction to practice and disclosure of drawings or structural chemical formulas: Applicants have claimed formulations and methods with an antifreeze protein antibody. It is not clear what this species is (note the rejection under 35 USC 112(b) below), but it is an antibody. Applicants mention an embodiment (as an antifreeze protein antibody) and mention where it was purchased, but give no information as to what its variable sequences are.
(c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure: Applicants have claimed a formulation and methods using a formulation comprising an antifreeze protein antibody. This is not clearly a specific antibody (such as Herceptin or Avastin). Nor is clearly a generic antibody with no binding specificity. An antibody described by what it binds to, without sufficient information to determine if a given antibody will bind to that structure, is not sufficient to meet the written description requirement (MPEP 2163(II)(A)(3)(a)); there must be enough structural information to determine if a given formulation meets the claim limitations.
Even if we knew what it bound to, it is not possible to determine the structure of the antibody a priori. Lowe (blog “In the pipeline” entry of 7 Sept, 2022) describes an experiment attempting to determine if a given compound will bind to a given protein. 39K compounds, including known antibiotics, were screened against E. coli for growth inhibition, finding 218 active compounds (1st page, 3d paragraph). These were computer docked to a set of 296 essential bacterial proteins by multiple docking procedures (1st page, 3d paragraph), along with 100 random inactive compounds from the screen (2nd page, 1st paragraph). The number of strong binders predicted were essentially the same between the active compounds and the controls, and out of 142 compound/target interactions previously known, the methodology found only 3 (2nd page, 2nd paragraph). While a given docking program may accurately predict if compound A binds to protein B, it is impossible to a priori know if the prediction is accurate. In other words, several years after applicant’s priority date, it was not possible to predict if a given compound and target bound to each other.
Nor is it possible to modify known sequences to reliably find new compounds. Guo et al (PNAS (2004) 101(25) p9205-9210) looked at the effect of random mutations (title). In a DNA repair enzyme, about one mutation in three killed the activity of the protein, consistent with studies with other proteins (abstract). Yampolsky et al (Genetics (2006) 170 p1459-1472), using a different methodology, found that even conservative substitutions were prone to problems (table 3, p1465, top of page). In other words, unless there is some information known about the binding, mutating the sequence is likely to be detrimental, making it a poor way to generate new compounds.
(d) representative number of samples: Applicants have not provided enough explanation to say what this antibody is, much less its structure. Even if applicants had given the sequence or other identifying characteristics of this antibody to uniquely identify it, given the unpredictability of modification, it is not possible to extrapolate from that theoretical antibody to all antibodies that can be used in the claims. Thus, the claims lack written description.
response to applicant’s arguments
Applicants argue that antibodies to antifreeze proteins are well known and commercially available.
Applicant's arguments filed 7 April, 2026 have been fully considered but they are not persuasive.
Applicants list two papers, one of which references the other, and point to a commercial source to argue that antibodies to antifreeze proteins are well known. Even if we interpret the claim language to be antibodies to antifreeze proteins (note rejection under 35 USC 112b, below), none of these references or the information about the commercially available antibodies provided by applicants provide any information about their variable regions, much less what features of these sequences are required for binding. Note that applicant’s arguments are very similar to those that failed to persuade the Supreme Court in Amgen v Sanofi (598 US 594).
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.
Claims 1-13 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.
The rejected claims require an antifreeze protein antibody. It is not clear what this means. Applicants have not defined the phrase, nor does a search in Google find this phrase used outside of this application. While it is improper to import limitations from the specification (MPEP 2111.01(II)), the interpretation must be consistent with the specification. The specification states that “In the present disclosure, the antifreeze protein antibody is further added to reduce an infection on PCR from the (antifreeze protein)” (p3, 1st paragraph). This suggests that the antibody is some sort of antimicrobial. However, Troisi et al (Front. Microbiol. (2022)13:1080059) states that an antibody has to hit a specific target on an microbe (2nd page, 1st column, 1st paragraph). That means that there is not a generic antimicrobial antibody. Nor does the antibody appear to be an anti-antifreeze protein antibody; that is not consistent with either the terminology used or how applicants are using the antibody, and an anti-infective.
The claims also have an antifreeze protein antibody of the type (I, II, III, or IV) antifreeze protein. It is not clear what this means. The plain meaning of the text is a protein that is both an antibody (to an unspecified target) and an antifreeze protein, but that is not consistent with applicant’s arguments or the text of the disclosure.
response to applicant’s arguments
Applicants argue that the claimed antibody is defined as an antibody that specifically binds to an antifreeze protein.
Applicant's arguments filed 7 April, 2026 have been fully considered but they are not persuasive.
A search for the key words antibody, bind, and antifreeze in applicant’s disclosure fail to find this definition. The closest thing to a definition is what is cited in the rejection; that the antibody is to reduce an infection. While not a definition, that is inconsistent with the definition that applicants are proposing.
Examiner’s Note
The concentrations in the claims are very low, and are odd units. Concentrations in solids are usually a percentage by weight or a mole fraction, not mg/L. Applicants require their antifreeze protein to be at 0.005-0.3 mg/L; note that Wu et al (cited by applicants) uses the antifreeze protein at 2.5 mg/mL (p417, 1st column, 6th paragraph). It is suspected that the concentrations given in the claims are of the solutions before lyophilization, not the concentrations after lyophilization (which is how the claim would be interpreted).
It is well known that freezing a protein can cause inactivation, especially when repeated, note Cao et al (Biotechnol. Bioeng. (2003) 82 p684-690), or the entry by “Daniel” on the Nucleics PCR forum page on 9 Nov, 2006. This provides an incentive to add an antifreeze protein to a PCR enzyme, to prevent freeze thaw cycles when cooled after reconstitution. Wu et al, cited by applicants, provides an incentive to add an antibody to the antifreeze protein to the mixture. Williams et al (J. Parenteral Sci. Technol. (1984) 38(2) p48-59) gives the general outline of the protocol of claim 7 (p48, 1st column, 3d paragraph). In other words, if we assume that the antibody is an anti-antifreeze antibody, the claims are obvious.
As it is not clear what is meant by an antifreeze protein antibody of an antifreeze protein, it is not possible to determine if there is support for this amendment. If there is not, it is new matter.
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
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