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 .
Applicant's response filed 7/24/2026 has been fully considered. The following rejections
and/or objections are either reiterated or newly applied.
Status of Claims
Claims 1-3, 5-21, and 23-32 pending and examined on the merits.
Claims 4 and 22 canceled.
Claims 29-32 newly added.
Priority
The instant application filed on 3/31/2022 is a Continuation of U.S. Application No. 18/570,580 filed on 12/14/2023, which is a 371 national stage entry of PCT/US2022/033437 having an international filing date of 6/14/2022, and claims the benefit of priority to provisional U.S. Application No. 63/210,905 filed on 6/15/2021. Thus, the effective filing date of the claims is 6/15/2021.
The applicant is reminded that amendments to the claims and specification must comply with 35 U.S.C. § 120 and 37 C.F.R. § 1.121 to maintain priority to an earlier-filed application. Claim amendments may impact the effective filing date if new subject matter is introduced that lacks support in the originally filed disclosure. If an amendment adds limitations that were not adequately described in the parent application, the claim may no longer be entitled to the priority date of the earlier filing.
Information Disclosure Statement
The IDS filed on 7/24/2026 and 7/28/2026 have been entered and considered. A signed copy of the corresponding 1449 forms have been included with this Office action.
Claim Objections
The objection to claim 28 withdrawn in view of Applicant's claim amendments filed on 7/24/2026.
Withdrawn Rejections
35 USC § 112(a)
The rejection of claims 1-26 and 28 under 35 USC 112(a) withdrawn in view of Applicant's claim amendments and remarks filed on 7/24/2026 (Remarks 7/24/2026 pages 1-6).
35 USC § 101
The rejection of claims 1-28 under 35 USC 101 withdrawn in view of Applicant's claim amendments and arguments regarding "improvements in the technical field of polypeptide optimization [. . .] namely, more robust laboratory-based analyses of sequence spaces", filed on 7/24/2026 (Remarks 7/24/2026 pages 9-15). Specifically, the interpretation of steps (a) through (e) as physical laboratory steps that are additional elements, when taken as a whole with the recited judicial exception of identifying a plurality of mutations in the first library of variant polypeptides based at least on one or more characteristic, is an improvement in a lab-based analysis of sequence spaces/library construction.
Claim Rejections - 35 USC § 112
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 1-3, 5-21, and 23-32 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. These rejections are newly recited and are necessitated by claim amendment.
Claims 1 and 27 recite steps (a) through (e) which consist of providing a first and second library of polynucleotides, processing these libraries, and identifying characteristics. It is not clear if these steps are being performed virtually in silico, or as physical steps in a laboratory. Even though there is an explicit used of "at least one processor" in step (f), this is not enough to disambiguate the two potential modes of operation for steps (a) through (e). To further prosecution, steps (a) through (e) are interpreted as being performed as physical steps in a laboratory for generating the data used in step (f).
Claim 28 recites steps (a) through (b) which consist of providing a first and second library of polynucleotides, processing these libraries, and identifying characteristics. It is not clear if these steps are being performed virtually in silico, or as physical steps in a laboratory. Even though there is an explicit used of "at least one processor" in step (c), this is not enough to disambiguate the two potential modes of operation for steps (a) through (b). To further prosecution, steps (a) through (b) are interpreted as being performed as physical steps in a laboratory for generating the data used in step (c).
Response to Arguments under 35 USC § 112
The rejection of claims 6-7, 12-13, 16, and 22 under 35 USC 112(b) withdrawn in view of Applicant's claim amendments and remarks filed on 7/24/2026. However, Applicant’s arguments regarding the rejection of claims 1 and 27-28 filed 7/24/2026 are fully considered but they are not persuasive.
Applicant notes that claims 1 and 27-28 have been amended to remove "computer-implemented" from the preamble of the independent claims, and further amended to recite "creating, using at least one processor, a training set…." in step (f) (claims 1 and 27) and step (c) (claim 28), and that these steps "clarify the hybrid nature of the claimed invention, namely the combination of laboratory-based data generation processes and computer-based data processing processes" (Remarks 7/24/2026 page 7). Examiner notes above in section "Claim Rejections - 35 USC 112" that even though there is an explicit used of "at least one processor" in the last limitation, this is not enough to disambiguate the two potential modes of operation for the previous steps.
Therefore, the rejection of claims 1 and 27-28 under 35 USC 112(b) is maintained. All other claims depend from these claims and therefore their rejection is likewise maintained.
Claim Rejections - 35 USC § 103
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.
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 1-3, 5-21, and 23-32 rejected under 35 U.S.C. 103 as being unpatentable over Whelihan et al. (WO-03048902) in view of Gustafsson et al. (US-7783428). The rejection of claims 1 and 27-28 contains newly recited portions necessitated by claim amendments, the rejection of claims 29-32 are newly recited necessitated by them being newly added claims, and the rest are previously recited.
Regarding claims 1 and 27-28, Whelihan teaches: providing a first library of polynucleotides encoding a first library of variant polypeptides; transcribing and translating the first library of polynucleotides to produce the first library of variant polypeptides (as interpreted above); and transcribing and translating the second library of polynucleotides to produce the second library of variant polypeptides (as interpreted above) (Page 15 line 8 "the invention features a method that includes constructing a first library of nucleic acids wherein each member of the first library includes one of a first limited set of codons at at least one varying position; constructing a second library of nucleic acids wherein each member of the second library includes one of a second limited set of codons at at least one varying position", and line 18 "The constructing can include synthesizing an oligonucleotide that comprises a region that is at least partially randomized, wherein the nucleotides of the region are synthesized by the addition of a trinucleotide from a mixture of trinucleotides, e.g., a limited set of trinucleotides. The codon usage at least one corresponding constant position can differs between nucleic acids of the first and second libraries").
Whelihan also teaches identifying a plurality of mutations in said first library of variant polypeptides based at least on one or more characteristics, wherein said one or more characteristics comprise an equilibrium binding constant, a kinetic binding constant, a protein stability measurement, an enzyme activity, a fractional activity, a nonspecific binding potential, an aggregation potential, a hydrophobicity, a protein expression level, or a maturation time of at least a portion of said first library of variant polypeptides (Page 6 line 3 "Assay information can also include structural assay information, for example, information about a biophysical or structural assay (e.g., protein stability or folding). The functional assay data can include, for each of a set of library members, binding activity for a first compound and binding activity for a second compound" and page 26 line 21 "The functional information 110 can relate to one or more of the following: a binding activity (including, for example, information related to specificity, a kinetic parameter, an equilibrium parameter, avidity, affinity, and so forth), a catalytic activity, a structural or biochemical property (e.g., thermal stability, oligomerization state, solubility and so forth), and a physiological property (e.g., renal clearance, toxicity, target tissue specificity, and so forth) and so forth").
Whelihan also teaches providing a second library of polynucleotides encoding a second library of variant polypeptides selected based at least on said plurality of mutations identified in (c) (Page 70 line 11 "A first display library is used to identify one or more ligands for a target. These identified ligands are then mutated to form a second display library. Higher affinity ligands are then selected from the second library").
Whelihan does not explicitly teach creating a training set comprising said second library of variant polypeptides, wherein a combinatorial sequence space of said second library of variant polypeptides is less than about 10%, less than about 1%, or less than about 0.1% of a combinatorial sequence space of said first library of variant polypeptides; nor at least one variant polypeptide of said second library of variant polypeptides comprises a mutation of said plurality of mutations comprising a neutral effect or a negative effect on a characteristic of said one or more characteristics.
However, Gustafsson teaches creating a training set comprising said second library of variant polypeptides, wherein a combinatorial sequence space of said second library of variant polypeptides is less than about 10%, less than about 1%, or less than about 0.1% of a combinatorial sequence space of said first library of variant polypeptides (Page 21 col 2 line 19 "The method of this aspect may be described by the following sequence of operations: (a) receiving data characterizing a training set of a protein variant library; (b) from the data, developing a sequence activity model that predicts activity as a function of amino acid residue type and corresponding position in the sequence" and filtering down to arbitrarily to any percent is obvious due to the potentially enormous combinatorial space of variant polypeptide libraries).
Gustafsson also teaches at least one variant polypeptide of said second library of variant polypeptides comprises a mutation of said plurality of mutations comprising a neutral effect or a negative effect on a characteristic of said one or more characteristics (page 39 col 1 line 47 "There are many computer programs available for searching and finding and motifs within a group of sequences. Typically, these programs are limited to characterizing sequences as part of a broad protein family or not. In the present invention, motif finding programs are used to characterize and predict the activity of proteins, e.g., artificially evolved proteins. For example, positive sequences (e.g., those having a desired level of fitness), negative sequences (e.g., those lacking a desired level of fitness), and parents are optionally entered into pattern finding programs separately").
Therefore, it would have been obvious to one of ordinary skill in the art as of the effective filing date of the claimed invention to use the selected training set of Whelihan for the training step of Gustafsson in order to identify amino acid residues for variation in a protein variant library to achieve a desired effect (Gustafsson page 21 col 2 line 13 "One aspect of the present invention pertains to methods, apparatus, and software for identifying amino acid residues for variation in a protein variant library. These residues are then varied in the sequences of protein variants in the library in order to affect a desired activity such as stability, catalytic activity, therapeutic activity, resistance to a pathogen or toxin, toxicity, etc"). One skilled in the art would have a reasonable expectation of success because both methods are concerned with screening variant protein libraries.
Regarding claims 2-3, 5-7, 12, and 27, Whelihan in view of Gustafsson teach the methods of Claim 1 on which this claim depends/these claims depend, respectively (with the exception of independent claim 27). Gustafsson also teaches: said second library of variant polypeptides comprises a variant polypeptide with an at least 10% improvement in at least one characteristic of said one or more characteristics compared to a reference polypeptide of said first library of variant polypeptides; at least 10% of said second library of variant polypeptides comprise said at least 10% improvement; said at least 10% improvement comprises an at least 10% decrease in said equilibrium binding constant; further comprising identifying said optimized polypeptide with said predictive algorithm; training, with said training set, said predictive algorithm to identify an optimized polypeptide; predictive algorithm is trained to predict a value of said one or more characteristics for a polypeptide; and said predictive algorithm is trained to identify an avidity-enhanced polypeptide from said third library of variant polypeptides (Section II named "Generating Improved Protein Variant Libraries" goes into detail regarding predicting desired improvements to various characteristics of a starting protein, specifically page 25 col 2 line 9 "Various criteria can be used to make this decision. Examples include the number of protein variant libraries generated so far, the activity of top proteins from the current library, the magnitude of activity desired, and the level of improvement observed in recent new libraries", and the magnitude of the improvement, and portion of a library that is improved would be a matter of optimization). The optimization of known parameters to achieve predictable results is considered routine and does not confer patentability (see MPEP 2144.05).
Regarding claims 8-9, Whelihan in view of Gustafsson teach the methods of Claim 7 on which this claim depends/these claims depend, respectively. Whelihan also teaches: said optimized polypeptide comprises an at least two-fold improvement in target affinity relative to a starting polypeptide; and said first library of variant polypeptides comprises a plurality of variants of said starting polypeptide (Page 53 line 25 "For example, if the proteins are all mutated variants of a single parental antibody or a set of known parental antibodies, variant amino acids at given positions can be identified that correlate with particular binding parameters, e.g., high affinity and slow K.sub.off" suggests comparison to a "starting polypeptide", the degree of which would be obvious as routine optimization).
Regarding claim 10, Whelihan in view of Gustafsson teach the methods of Claim 7 on which this claim depends/these claims depend, respectively. Gustafsson also teaches said optimized polypeptide is absent from said first and second libraries of variant polypeptides (Page 40 col 1 line 21 "step J2 includes determining a number of times the one or more motifs occur in or are absent from the two or more members of the population of polypeptide character string variants" suggests a motif may be absent from the training data).
Regarding claim 11, Whelihan in view of Gustafsson teach the methods of Claim 7 on which this claim depends/these claims depend, respectively. Given the vast combinatorial sequence space, it is guaranteed to cover proteins that have tandem repeats, in addition to them accounting for over one tenth of all known proteins as evidenced by Pellegrini (Frontiers in bioengineering and biotechnology 3 (2015): 143): page 1 intro paragraph 2 "They have been detected in about 14% of all the then known proteins, with eukaryotic proteins being three times more as likely to have internal repeats than prokaryotic ones"
Regarding claims 13-14 and 16, Whelihan in view of Gustafsson teach the methods of Claim 1 on which this claim depends/these claims depend, respectively. Gustafsson also teaches: generating a plurality of combinations of said plurality of mutations, and wherein at least a portion of said second library of variant polypeptides comprises said plurality of combinations; wherein a combination of said plurality of mutations comprises a combination of a mutation of a first variant polypeptide and a mutation of a second variant polypeptide to form a variant polypeptide of said second library of variant polypeptide; and said plurality of combinations of said plurality of mutations comprises at least about 90% of all combinations of said plurality of mutations (Page 21 col 2 line 36 "The protein variant library may include proteins from various sources. In one example, the members include naturally occurring proteins such as those encoded by members of a single gene family. In another example, the members include proteins obtained by using a recombination-based diversity generation mechanism. Classical DNA shuffling (i.e., DNA fragmentation-mediated recombination) or synthetic DNA shuffling (i.e., synthetic oligonucleotide-mediated recombination) may be performed on nucleic acids encoding all or part of one or more naturally occurring parent proteins for this purpose"). Again, routine optimization and simply applying a combinatorial approach to the shuffling of Gustafsson would be obvious
Regarding claim 15, Whelihan in view of Gustafsson teach the methods of Claim 1 on which this claim depends/these claims depend, respectively. Whelihan also teaches said first library of variant polypeptides comprises polypeptides with one or more amino acid substitutions, one or more amino acid deletions, one or more amino acid insertions, one or more fusion polypeptides, or any combination thereof (Page 13 line 2 "In another example, each member of the library encodes a protein that includes a Kunitz domain, and the display library includes at least 10 different sequence variants of the Kunitz domain, h still another example, each member of the library encodes a protein that includes an amino acid sequence that includes a varied region of less than50, 40, 30, or 20 amino acids, the varied region including at least 4, 8, 12, or 18 varied positions" as variants cover at least substitutions, insertions, and deletions).
Regarding claims 17-18, Whelihan in view of Gustafsson teach the methods of Claim 1 on which this claim depends/these claims depend, respectively. Whelihan also teaches one or both of said first and second libraries of variant polypeptides comprises an affinity-improved (and avidity-improved) variant of a starting polypeptide (Whelihan suggests binding affinity and avidity as functional information to be tested, therefore it would have been obvious to include this parameter for optimization).
Regarding claim 19, Whelihan in view of Gustafsson teach the methods of Claim 1 on which this claim depends/these claims depend, respectively. Gustafsson also teaches said second library of variant polypeptides is selected based on a multiplexed value of at least two of said one or more characteristics (Page 23 col 1 line 56 " "Selection" refers to the process in which one or more bio-molecules are identified as having one or more properties of interest. Thus, for example, one can screen a library to determine one or more properties of one or more library members. If one or more of the library members is/are identified as possessing a property of interest, it is selected. Selection can include the isolation of a library member, but this is not necessary. Further, selection and screening can be, and often are, simultaneous").
Regarding claims 20-21, Whelihan in view of Gustafsson teach the methods of Claim 1 on which this claim depends/these claims depend, respectively. Gustafsson also teaches: said training set further comprises a third library of variant polypeptides; and a polypeptide of said second library of variant polypeptides varies from a starting polypeptide by a first mutation process and a polypeptide of said third library of variant polypeptides varies from said starting polypeptide by a second mutation process (Page 24 col 2 line 21 "As shown, a process 01 begins at a block 03 with receipt of data describing a training set comprising residue sequences for a protein variant library. In other words, the training set data is derived from a protein variant library. Typically that data will include, for each protein in the library, a complete or partial residue sequence together with an activity value. In some cases, multiple types of activities (e.g., rate constant and thermal stability) are provided together in the training set", while not explicitly calling out a third library, or the differences between differing sets of mutated proteins, it would be obvious that the proteins of each library would be different from one another, otherwise the information would be redundant).
Regarding claim 23, Whelihan in view of Gustafsson teach the methods of Claim 20 on which this claim depends/these claims depend, respectively. Gustafsson also teaches said third library of variant polypeptides comprises a plurality of polypeptides excluded from said second library of variant polypeptides, and wherein said plurality of polypeptides excluded from said second library of variant polypeptides comprise a target affinity less than those included in said second library of variant polypeptides (Page 70 line 1 "One purpose for distinguishing among component libraries of a composite library is to for quality control. After display library members from a composite library are analyzed and sequenced, the originating component library for each library member is determined. Then, the number of useful identified display library members can be counted for each component library. Also, the frequency of insertions and deletions can be estimated for each component library. These statistics can be used to identify sub-optimal component libraries. Such libraries can be omitted from subsequently poolings for composite libraries" suggests excluding certain components from libraries; and Page 24 col 1 line 63 Section II named "Generating Improved Protein Variant Libraries" goes into detail regarding predicting desired improvements to various characteristics of a starting protein, specifically page 25 col 2 line 9 "Various criteria can be used to make this decision. Examples include the number of protein variant libraries generated so far, the activity of top proteins from the current library, the magnitude of activity desired, and the level of improvement observed in recent new libraries", suggests improving a desired characteristic, and combining with Whelihan from instant claim 22 would be obvious to exclude certain proteins with less desired characteristics).
Regarding claim 24, Whelihan in view of Gustafsson teach the methods of Claim 1 on which this claim depends/these claims depend, respectively. Gustafsson also teaches said identifying one or more characteristics comprises performing a polypeptide stability assay under a plurality of pH or temperature conditions (Page 24 col 2 line 37 "Activity data may be obtained by assays or screens appropriately designed to measure activity magnitudes. Such techniques are well known and are not central to this invention. The principles for designing appropriate assays or screens are widely understood" renders the claim obvious because testing protein stability using the methods of Whelihan using multiple parameter conditions is a well-known assay design).
Regarding claim 25, Whelihan in view of Gustafsson teach the methods of Claim 1 on which this claim depends/these claims depend, respectively. Gustafsson also teaches said predictive algorithm comprises a machine learning algorithm (Page 27 col 2 line 10 "In a preferred embodiment of the present invention, the sequence activity model is a partial least squares (PLS) variable regression model. PLS is an algorithm that uses X (independent) variable importance regression to build predictive models based on multicollinearity among variables and their correlation with a Y-score (i.e., dependent variable). The X- and Y-scores are selected by PLS so that the relationship of successive pairs of X and Y scores is as strong as possible").
Regarding claim 26, Whelihan in view of Gustafsson teach the methods of Claim 1 on which this claim depends/these claims depend, respectively. As evidenced by Zhang (Trends in Genetics 16.3 (2000): 107-109), protein lengths range from dozens to thousands of amino acid residues, therefore it would be obvious to include at least 10^6 variant polypeptides in a screening library, as it would only take a length of 5 amino acids to have a combinatorial sequence space greater than 10^6, and a length of just a single dozen (let alone dozens) has a combinatorial sequence space of over four quadrillion.
Regarding claim 29, Whelihan in view of Gustafsson teach the methods of Claim 1 on which this claim depends/these claims depend, respectively. Whelihan also teaches said plurality of mutations comprises at least one amino acid substitution (page 13 line 2 "In another example, each member of the library encodes a protein that includes a Kunitz domain, and the display library includes at least 10 different sequence variants of the Kunitz domain, h still another example, each member of the library encodes a protein that includes an amino acid sequence that includes a varied region of less than50, 40, 30, or 20 amino acids, the varied region including at least 4, 8, 12, or 18 varied positions" as variants cover at least substitutions, insertions, and deletions).
Regarding claim 30, Whelihan in view of Gustafsson teach the methods of Claim 1 on which this claim depends/these claims depend, respectively. Whelihan also teaches said first library of variant polypeptides is attached to said first library of polynucleotides by a polypeptide display method, said second library of variant polypeptides is attached to said second library of polynucleotides by said polypeptide display method, or both (page 57 line 10 "One format utilizes viruses, particularly bacteriophages. This format is termed "phage display." The varied polypeptide component is typically covalently linked to a bacteriophage coat protein or domain thereof. The linkage can be produced by a translational fusion encoded by a nucleic acid, and joining the varied polypeptide and the invariant bacteriophage coat protein or domain thereof").
Regarding claim 31, Whelihan in view of Gustafsson teach the methods of Claim 1 on which this claim depends/these claims depend, respectively. Whelihan also teaches said one or more characteristics comprises said equilibrium binding constant or said kinetic binding constant (page 26 line 21 "The functional information 110 can relate to one or pmore of the following: a binding activity (including, for example, information related to specificity, a kinetic parameter, an equilibrium parameter, avidity, affinity, and so forth), a catalytic activity, a structural or biochemical property (e.g., thermal stability, oligomerization state, solubility and so forth), and a physiological property (e.g., renal clearance, toxicity, target tissue specificity, and so forth) and so forth").
Regarding claim 32, Whelihan in view of Gustafsson teach the methods of Claim 1 on which this claim depends/these claims depend, respectively. Whelihan also teaches said characteristic of said one or more characteristics comprises said protein stability measurement (page 6 line 3 "Assay information can also include structural assay information, for example, information about a biophysical or structural assay (e.g., protein stability or folding)").
Response to Arguments under 35 USC § 103
Applicant’s arguments filed 7/24/2026 are fully considered but they are not persuasive.
Applicant asserts, regarding the amended claim 1, that "neither Whelihan nor Gustafsson appear to teach, disclose, or suggest identifying a mutation 'comprising a neutral effect or a negative effect on a characteristic of said one or more characteristics' for inclusion in 'at least one variant polypeptide of said second library of variant polypeptides'" (Remarks 7/24/2026 pages 15-18). Examiner notes that Gustafsson does in fact teach identifying mutations with negative effects (page 39 col 1 line 47 "There are many computer programs available for searching and finding and motifs within a group of sequences. Typically, these programs are limited to characterizing sequences as part of a broad protein family or not. In the present invention, motif finding programs are used to characterize and predict the activity of proteins, e.g., artificially evolved proteins. For example, positive sequences (e.g., those having a desired level of fitness), negative sequences (e.g., those lacking a desired level of fitness), and parents are optionally entered into pattern finding programs separately").
Therefore, the rejection of claims 1-3, 5-21, and 23-28 under 35 USC 103 is maintained, and the rejection of claims 29-32 under 35 USC 103 are newly made, above.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 5-21, and 23-32 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent Application 18/570,580. The following provisional nonstatutory double patenting rejection is newly cited and necessitated by amendments filed 7/24/2026. Although the claims at issue are not identical, they are not patentably distinct from each other because both are high throughput methods for identifying an optimized polypeptide, including: providing a first and second library of polynucleotide library and processing them to produce a first and second library of variant polypeptides attached to said first and second library of polynucleotides, identifying mutations of the first library of variant polypeptides, identifying mutations comprising negative effects on a characteristic, and creating a filtered data set of (optimized data) variant polypeptides.
Claims 1-3, 5-21, and 23-32 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent Application 19/552,778 in view of Gustafsson et al. (US-7783428). The following provisional nonstatutory double patenting rejection is newly cited and necessitated by amendments filed 7/24/2026. Although the claims at issue are not identical, they are not patentably distinct from each other because both are high throughput methods for identifying an optimized polypeptide, including: providing a first and second library of polynucleotide library and processing them to produce a first and second library of variant polypeptides attached to said first and second library of polynucleotides, identifying mutations of the first library of variant polypeptides, and creating a filtered data set of (optimized data) variant polypeptides.
While 19/552,778 does not explicitly teach identifying mutations comprising negative or neutral effects on a characteristic, it would have been obvious to one of ordinary skill in the art to modify these methods, with those taught by Gustafsson as described above for claim 1 of the instant application (Gustafsson teaches creating a training set comprising said second library of variant polypeptides, wherein a combinatorial sequence space of said second library of variant polypeptides is less than about 10%, less than about 1%, or less than about 0.1% of a combinatorial sequence space of said first library of variant polypeptides (Page 21 col 2 line 19 "The method of this aspect may be described by the following sequence of operations: (a) receiving data characterizing a training set of a protein variant library; (b) from the data, developing a sequence activity model that predicts activity as a function of amino acid residue type and corresponding position in the sequence" and filtering down to arbitrarily to any percent is obvious due to the potentially enormous combinatorial space of variant polypeptide libraries). Gustafsson also teaches at least one variant polypeptide of said second library of variant polypeptides comprises a mutation of said plurality of mutations comprising a neutral effect or a negative effect on a characteristic of said one or more characteristics (page 39 col 1 line 47 "There are many computer programs available for searching and finding and motifs within a group of sequences. Typically, these programs are limited to characterizing sequences as part of a broad protein family or not. In the present invention, motif finding programs are used to characterize and predict the activity of proteins, e.g., artificially evolved proteins. For example, positive sequences (e.g., those having a desired level of fitness), negative sequences (e.g., those lacking a desired level of fitness), and parents are optionally entered into pattern finding programs separately")), in order to identify amino acid residues for variation in a protein variant library to achieve a desired effect (para.9 "One aspect of the present invention pertains to methods, apparatus, and software for identifying amino acid residues for variation in a protein variant library. These residues are then varied in the sequences of protein variants in the library in order to affect a desired activity such as stability, catalytic activity, therapeutic activity, resistance to a pathogen or toxin, toxicity, etc"). One skilled in the art would have a reasonable expectation of success because both methods are concerned with screening variant protein libraries.
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 TH REE-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 finaI action.
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/R.A.P./Examiner, Art Unit 1686
/KAITLYN L MINCHELLA/Primary Examiner, Art Unit 1685
