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 .
Priority
This application 17/300,940 filed on 12/15/2021 claims the benefit of provisional U.S. Patent Application No. 63/125,904, filed on 12/15/2020.
The priority date of claims 1-3, 6-8, 14, 17, 21, 32, 52- 53, and 113 is determined to be 12/15/2020, the filing date of provisional U.S. Patent Application No. 63/125,904.
The priority date of dependent claims 4, 18-20 and 56 is determined to be 12/15/2021, the filing date of the instant application 17/300,940 because the provisional U.S. Patent Application No. 63/125,904 does not fully support the limitations recited in the claims filed on 12/15/2021.
Status of Claims
Applicant’s amendments to claims filed 04/20/2026 in response to the Non-Final Rejection mailed 10/21/2025 are acknowledged.
Claims 1, 52, 56, and 113 are amended.
Claims 51 and 171 have been canceled.
Claims 1-4, 6-8, 14-21, 32, 52-53, 56, and 113 are pending and under examination.
Response to Remarks filed 04/20/2026
The amendments and arguments presented in the papers filed 04/20/2026 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 10/21/2025 listed below have been reconsidered as indicated.
a) The objections to the specification regarding the language of the abstract are withdrawn in view of the amendments to the abstract.
b) The rejection of claims 1-4, 6-8, 14-21, 32, 51-53, 56, 113, and 171 under 35 35 U.S.C. 101 are modified in view of arguments and amendments to the claims.
c) The rejection of claims 1, 7, 8, 14, 32, 51, and 171 under 35 U.S.C. 102 as being anticipated by Wade et al. are withdrawn in view of the amendments to the claims and the cancellation of claims 51 and 171.
d) The rejection of (i) claims 1-4, 6, 52, 53, and 113 under 35 U.S.C. 103 as being unpatentable over Wade et al. and Ramachandran et al.; (ii) claims 14-21 under 35 U.S.C. 103 as being unpatentable over Wade et al. and Shen et al; and (iii) claim 56 under 35 U.S.C. 103 as being unpatentable over Wade et al. and Ramachandran et al. are withdrawn or modified in view of the amendments to the claims.
New and modified grounds of rejection necessitated by amendment are detailed below and this action is made FINAL.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-4, 6-8, 14-21, 32, 52-53, 56, and 113 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106, part II.
Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility.
This maintained rejection has been modified to address arguments and claim amendments filed on 04/20/2026.
Step 1
The claimed invention is directed to the statutory category of a process.
Step 2A, Prong One
The claims are taken to be directed to an abstract idea, a judicial exception.
Claim 1 is directed to a method comprising “determining the identity of the molecular barcode based on a barcode-specific pattern in the series of signal pulses”. These limitations are abstract mental processes (see MPEP 2106.04(a)(2)(III)). As written, the “determining” step encompasses the mental steps of looking at data, for example in a report or on a screen, and making mental judgements.
Claims 2-4, 6-8, 14-21, 32, 52-53, and 113 depend from claim 1, and require the same steps of “detecting a series of signal pulses” and “determining the identity of the molecular barcode”.
Claim 56 is directed to a method comprising “determining the identity of the molecular barcode based on a barcode-specific pattern in the series of signal pulses”. These limitations are abstract mental processes (see MPEP 2106.04(a)(2)(III)). As written, the “determining” step encompasses the mental steps of looking at data, for example in a report or on a screen, and making mental judgements.
Step 2A, Prong Two
The exception is not integrated into a practical application of the exception. The claims do not recite any additional elements that integrate the exception into a practical application of the exception.
While claim 1 recites “contacting a molecular barcode with a barcode recognition molecule that binds to one or more sites on the molecular barcode, wherein the molecular barcode is attached to an analyte comprising a biomolecule”, this is not an integration of the exception into a practical application. Instead, this element is data gathering required to perform the method.
Furthermore, while claim 32 recites the additional step of “contacting the molecular barcode with two or more barcode recognition molecules—” and claim 113 recites the additional step of “sequencing the biomolecule by subjecting the biomolecule to sequencing reaction conditions”, these are not integrations of the exception into a practical application. Rather, these “contacting”, “sequencing, steps are mere data collection and data analysis required to perform the method. (See MPEP 2106.04(a)(2)(III); claims to "collecting information, analyzing it, and displaying certain results of the collection and analysis," where the data analysis steps are recited at a high level of generality such that they could practically be performed in the human mind, Electric Power Group v. Alstom, S.A., 830 F.3d 1350, 1353-54, 119 USPQ2d 1739, 1741-42 (Fed. Cir. 2016).
While claim 52 recites “contacting the polypeptide with one or more terminal amino acid recognition molecules”, this is not an integration of the exception into a practical application. Instead, this element is data gathering required to perform the method.
While claim 56 recites “contacting a molecular barcode with a barcode recognition molecule that binds to one or more sites on the molecular barcode, wherein the molecular barcode is attached to an analyte, wherein an enzyme is bound to the analyte”, this is not an integration of the exception into a practical application. Instead, this element is data gathering required to perform the method.
Step 2B
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception. The claim does not add a specific limitation other than what is well-understood, routine, and conventional in the field. Steps directed to “contacting” two molecules and “sequencing” are techniques that are routine, conventional, and well-known in the art as demonstrated in the 103 rejections documented below. For these reasons, the claims are rejected under section 101 as being directed to non-statutory subject matter.
Response to Arguments against Claim Rejection - 35 U.S. C § 101
The response asserts that the amended claims do not recite an abstract idea because they recite steps that cannot practically be performed in the human mind. For example, claims 1 and 56 recites steps of including "contacting a molecular barcode with a barcode recognition molecule", "detecting a series of signal pulses indicative of binding interactions between the barcode recognition molecule and the molecular barcode" and "sequencing the polypeptide” (p. 9). The response further asserts that the abstract idea is integrated into a practical application arguing that the claims of the present application improve the field of molecular analysis by leveraging barcoding principles in conjugation with advancements in single molecule analysis, allowing discrete binding events to be monitored in real-time (p. 9).
Applicant's arguments have been fully considered but are not persuasive.
While it is agreed that the steps of detecting single molecular kinetics cannot practically be performed in the human mind, the determining step remains an abstract idea. Specifically, as described above in the 101 rejection, claims 1 and 56 remain directed to a limitation comprising “determining the identity of the molecular barcode”. This step encompasses mental steps of looking at a readout of signal pulse patterns and assigning an identity, a process that can be accomplished in the human mind.
The response further asserts that the amended claims integrate any abstract idea into a practical application. The response further asserts that the claims of the present application improve the field of molecular analysis and amended claims 1 and 56 recite steps that allow discrete binding events to be monitored in real-time –[by] detecting a series of signal pulses indicative of binding interactions between the barcode recognition molecule and the molecular barcode (p. 9).
Applicant's arguments have been fully considered but are not persuasive.
Steps of "contacting a molecular barcode with a barcode recognition molecule that binds to one or more sites on the molecular barcode, wherein the molecular barcode is attached to an analyte comprising a polypeptide; detecting a series of signal
pulses indicative of binding interactions between the barcode recognition molecule and the molecular barcode” are necessary data gathering steps that are consider routine and conventional in the art. These steps are required to provide the data for the method and are not integrations of the exception into a practical application.
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 1-4, 6-8, 14, 32, 56, and 113 are rejected under 35 U.S.C. 103 as being unpatentable over Wade et al. (124-Color Super-resolution Imaging by Engineering DNA-PAINT Blinking Kinetics. Nano Lett. 2019. 19(4):2641-2646) in view of Ramachandran et al. (WO2020/123309, on IDS dated 03/10/2023).
The following are new and modified rejections necessitated by claim amendments filed on 04/20/2026.
Regarding claim 1, Wade teaches using the method of DNA-PAINT, the method comprising short dye-labeled oligonucleotides, i.e. DNA-PAINT imager strands, (barcode recognition molecules) that bind transiently to complementary DNA molecule DNA-Paint docking strands (molecular barcodes) that are bound to a target (analyte comprising a biomolecule) (p. 2642, col. 1 and Fig. 1). Wade teaches using the method for protein detection, with a protein (polypeptide) as a target (analyte) (p. 2641, Abstract and Fig. 2).Wade teaches that binding kinetics such as blinking frequency and duration can be tuned precisely and used downstream as “barcodes” for detection (p. 2642, col1. 1), i.e. detecting a series of signal pulses indicative of binding interactions between the barcode recognition molecule and the molecular barcode. Wade teaches changing the length of the docking strand (molecular barcode) or number of binding sites to perform combinatorial barcoding (p. 2642, cols 1 and 2 and Fig. 1). Wade further teaches determining the identity of two different barcodes by blinking frequency (a barcode-specific pattern in the series of signal pulses) (p. 2643, col. 2 and Fig. 2).
Wade does not teach sequencing the polypeptide.
Ramachandran teaches a method of capturing and characterizing analytes comprising: capture probes that include a capture domain (for capturing an analyte) and a universal molecular identifier (UMI) (molecular barcode) (p. 7, lines 24-26). Ramachandran teaches the sequence of the captured polypeptide is determined through detection of amino acid residues labeled with a detectable label) (p. 239, lines 3-6), satisfying the requirement of sequencing the polypeptide. Ramachandran teaches permeabilizing a sample before analyte capture (Fig. 4), including options of selective permeabilization or selective lysing that can permeabilize a membrane of a subcellular region while leaving a different subcellular region substantially intact for any analytes of interest (p. 62, lines 4-13).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Wade and Ramachandran to arrive at the instantly claimed invention. The modification would have entailed adding the additional step of sequencing the captured polypeptide of Wade using the method of Ramachandran to lyse cells and capture analytes (polypeptides) for sequencing. One would have been motivated to sequence the polypeptide in order to confirm the identify the polypeptide of Wade in addition to identifying the identity of the docking strand (molecular barcode) as in Wade, furthering Wade’s stated goal of protein detection (p. 1, Abstract). There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claims 2-4, and 6, Wade does not teach the analyte is immobilized to a surface through the molecular barcode (claim 2); the molecular barcode is immobilized to the surface through a linkage group comprising at least one biomolecule (claim 3); the linkage group of claim 3 comprises a double-stranded nucleic acid and/or a protein-ligand complex (claim 4); or wherein the linkage group of claim 3 comprises: a double-stranded nucleic acid comprising a bis-biotin moiety, wherein the double-stranded nucleic acid is attached to the molecular barcode; and an avidin protein bound to the bis-biotin moiety, wherein the avidin protein is attached to the surface (claim 6).
Regarding claim 2, Ramachandran teaches a method of capturing and characterizing analytes comprising: capture probes that include a capture domain (for capturing an analyte) and a universal molecular identifier (UMI) (molecular barcode) (p. 7, lines 24-26). Capture probes (molecular barcodes) can be attached to a surface (p. 18, line 12), i.e. immobilized to a surface.
Regarding claim 3, Ramachandran teaches embodiments in which a capture probe does not bind directly to the substrate, but interacts indirectly, for example by binding to a molecule which itself binds directly or indirectly to the substrate (p. 129, lines 19-25), as encompassed by the requirement of immobilization to the surface through a linkage group comprising at least one biomolecule.
Regarding claim 4, Ramachandran teaches ligating additional oligonucleotides to an in situ synthesized oligonucleotide to generate a capture probe. For example, hybridizing an additional oligonucleotide and extending to form a double stranded oligonucleotide (double-stranded linkage group) and to further create a 3’ overhang (molecular barcode) (p. 95, lines 26-31). Thus, Ramachandran teaches a molecular barcode (here a capture probe) that has a double stranded region (double-stranded nucleic acid as a linkage group) in addition to a single stranded overhang (barcode region).
Regarding claim 6, Ramachandran teaches affinity groups including biotin and avidin (p. 28, lines 4-9) and that the affinity group can be coupled to an array feature specific for the affinity group (p. 99, lines 8-11). For example, the array feature (surface) includes avidin or streptavidin and the affinity group includes biotin (p. 99, lines 8-11). Ramachandran further teaches using biotinylated oligonucleotides (capture probes/molecular barcodes) with sequence complementary to one or more analytes that can be selected using biotinylation-strepavidin affinity (p. 241, lines 29-31). Thus Ramachandran satisfies the requirements of molecular barcodes labeled with biotin that can be coupled to avidin attached to a surface.
Neither Wade nor Ramachandran teach a bis-biotin moiety.
However, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Wade and Ramachandran to arrive at the instantly claimed invention. The modification would have entailed using the method of attachment of Ramachandran for capture probes to attach the barcode attached to an analyte of Wade to a surface. The capture probes of Ramachandran bind an analyte and comprise a molecular barcode, thus serving an analogous purpose as the docking strands of Wade. One would have been motivated to use the attachment of Ramachandran in order to secure the docking strand and analyte of Wade in order to have a fixed position for imaging of the signal pulses for each analyte and barcode. The modification would further have entailed using a bis-biotin moiety as the biotin moiety used for the affinity group. Selecting biotin or other affinity groups is routine and conventional in the art and would have been a matter of routine optimization. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 7, Wade teaches DNA molecule docking strands (molecular barcodes) (p. 2642, col. 1 and Fig. 1).
Regarding claim 8, Wade teaches short dye-labeled oligonucleotides, i.e. DNA-PAINT imager strands, (barcode recognition molecules) (p. 2642, col. 1 and Fig. 1).
Regarding claim 14, Wade teaches using the short dye-labeled oligonucleotide
imager strands (barcode recognition molecules comprising a detectable label) (p. 2642, col.1 and Fig. 1A).
Regarding claim 32, Wade teaches a docking strand (molecular barcode) with more than one binding domain contacted by dye-labeled oligonucleotides, i.e. DNA-PAINT imager strands, (barcode recognition molecules) that bind to the domains (Fig. 2).
Regarding claim 56, Wade teaches using the method of DNA-PAINT, the method comprising short dye-labeled oligonucleotides, i.e. DNA-PAINT imager strands, (barcode recognition molecules) that bind transiently to complementary DNA molecule DNA-Paint docking strands (molecular barcodes) that are bound to a target (analyte comprising a biomolecule) (p. 2642, col. 1 and Fig. 1). Wade teaches using the method for protein detection, with a protein (polypeptide) as a target (analyte) (p. 2641, Abstract and Fig. 2).Wade teaches that binding kinetics such as blinking frequency and duration can be tuned precisely and used downstream as “barcodes” for detection (p. 2642, col1. 1), i.e. detecting a series of signal pulses indicative of binding interactions between the barcode recognition molecule and the molecular barcode. Wade teaches changing the length of the docking strand (molecular barcode) or number of binding sites to perform combinatorial barcoding (p. 2642, cols 1 and 2 and Fig. 1). Wade further teaches determining the identity of two different barcodes by blinking frequency (a barcode-specific pattern in the series of signal pulses) (p. 2643, col. 2 and Fig. 2).
Wade does not teach wherein an enzyme is bound to the analyte (comprising a polypeptide) or sequencing the polypeptide.
Ramachandran teaches a method of capturing and characterizing analytes comprising capture probes that include a capture domain (for capturing an analyte) and a universal molecular identifier (UMI) (molecular barcode) (p. 7, lines 24-26). Ramachandran teaches the sequence of the captured polypeptide is determined through detection of amino acid residues labeled with a detectable label) (p. 239, lines 3-6), satisfying the requirement of sequencing the polypeptide. Ramachandran further teaches HRP (an enzyme) may be a detectable label (p. 31, lines 7-10), and that detectable labels may bf attached to a composition to be detected (analyte) (p. 29, lines 11-12).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Wade and Ramachandran to arrive at the instantly claimed invention. The modification would have entailed adding enzymes as in Ramachandran to the biological sample that could attach to the captured analyte of Wade. The modification would have entailed adding the detectable label of HRP to the analyte. One would have been motivated to do so in order to perform addition molecular operations using the enzyme such as for the detection of amino acid residues for sequencing. The modification would have further entailed adding the additional step of sequencing the captured polypeptide of Wade using the method of Ramachandran to lyse cells and capture analytes (polypeptides) for sequencing. One would have been motivated to sequence the polypeptide in order to confirm the identify the polypeptide of Wade in addition to identifying the identity of the docking strand (molecular barcode) as in Wade, furthering Wade’s stated goal of protein detection (p. 1, Abstract). There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 113, Wade does not teach sequencing the biomolecule by subjecting the biomolecule to sequencing reaction conditions.
Ramachandran teaches the sequence of the captured polypeptide is determined through detection of amino acid residues labeled with a detectable label) (p. 239, lines 3-6), satisfying the requirement of subjecting the polypeptide to sequencing reaction conditions.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Wade and Ramachandran to arrive at the instantly claimed invention. The modification would have entailed adding the additional step of sequencing the captured polypeptide of Wade using the method of Ramachandran. Performing the method of sequencing of a polypeptide as taught by Ramachandran requires subjecting the polypeptide to sequencing reaction conditions. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Claims 15-21 are rejected under 35 U.S.C. 103 as being unpatentable over Wade et al. (124-Color Super-resolution Imaging by Engineering DNA-PAINT Blinking Kinetics. Nano Lett. 2019. 19(4):2641-2646) in view of Ramachandran et al. (WO2020/123309, on IDS dated 03/10/2023) as applied to claims 1-4, 6-8, 14-21, 32, 52-53, 56, and 113 above, further in view of Shen et al. (US PGPub 20170184580).
These are new rejections necessitated by claim amendments filed on 04/20/2026.
Regarding claims 15-21, neither Wade nor Ramachandran teach the barcode recognition molecule is attached to a labeled biomolecule comprising the at least one detectable label (claim 15); wherein the labeled biomolecule is a labeled nucleic acid (claim 16); wherein the barcode recognition molecule is attached to the labeled biomolecule through a linkage group comprising at least one biomolecule (claim 17); wherein the linkage group comprises a protein-ligand complex (claim 18); wherein the protein-ligand complex comprises a multivalent protein comprising at least two ligand binding sites, wherein the barcode recognition molecule comprises a first ligand moiety bound to a first ligand binding site on the multivalent protein, and wherein the labeled biomolecule comprises a second ligand moiety bound to a second ligand binding site on the multivalent protein (claim 19); wherein the multivalent protein is an avidin protein comprising four biotin binding sites, and wherein the ligand moieties are biotin moieties (claim 20); or wherein at least one of the biotin moieties is a bis-biotin moiety, and wherein the bis-biotin moiety is bound to two biotin binding sites on the avidin protein (claim 21).
Shen teaches bis-biotinylation tags for labeling. Shen teaches bis-biotin tags covalently coupled to a molecule (barcode recognition molecule), with the bis-biotin tag bound to a tetravalent biotin-binding agent (avidin linkage group) that is in turn bound to a second bis-biotin moiety (para 12 and Fig. 2). Shen teaches any desired molecule can be joined, including oligonucleotides and nucleic acids (para 12), and that biotin-streptavidin interactions can be used for linking different molecules together (para 9).
Regarding claim 15, Shen teaches joining desired molecules including oligonucleotides (e.g. a barcode recognition molecule) and labels (para 12), and that both are considered reactants of interest (para 50).
Regarding claim 16, Shen teaches a reactants include nucleic acids and fluorescent labels (para 18).
Regarding claim 17, Shen teaches a reactant of interest can be any molecule, including oligonucleotides and nucleic acids (para 50). She further teaches a reactant of interest (barcode recognition molecule) attached to a detectable label (labeled biomolecule) via streptavidin (linkage group) (Fig. 2).
Regarding claim 18, Shen teaches linking a labeled molecule to a reactant of interest via bis-biotin tags (ligands) bound to a tetravalent biotin-binding agent (protein) (para 12 and Fig. 2), thus forming a linkage group comprising a protein-ligand complex).
Regarding claim 19, Shen teaches tetravalent biotin-binding agent (a multivalent protein comprising at least two ligand binding sites) (para 8). Shen further teaches a reactant of interest (barcode recognition molecule) with biotin (a first ligand moiety) bound to streptavidin (multivalent protein) in a first site and a detectable label (labeled biomolecule) with biotin (a second ligand moiety) bound to streptavidin (multivalent protein) in a second site (Fig. 2).
Regarding claim 20, Shen teaches tetravalent biotin-binding agents include avidin (para 8).
Regarding claim 21, Shen teaches two bis-biotin moieties bound to two binding sites on streptavidin (Fig. 2). Shen also teaches the use of avidin in place of streptavidin (para 56).
Shen states that the use of bis-biotin tags provides advantages for labeling and detection (para 114).
Shen does not teach the nucleic acid is labeled.
However, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Wade and Ramachandran with Shen to arrive at the instantly claimed invention. Regarding the labeling of the nucleic acid, such labeling was well known and routine in the art at the time of filing, as shown by the imager strand labeling of Wade. The modification would have entailed using the bis-biotin modifications and avidin linkage to indirectly label the imager strand (barcode recognition molecule) of Wade. One would have been motivated to make the modifications by the modularity provided by the use of an avidin linker. In particular, one would have been motivated by the stable binding provided by the use of multi-biotin tagging and avidin (Shen, para 75). The use of biotin and biotin-binding agents to couple molecules was well known and routine in the art before the effective filing date of the claimed invention. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Claims 52 and 53 are rejected under 35 U.S.C. 103 as being unpatentable over Wade et al. (124-Color Super-resolution Imaging by Engineering DNA-PAINT Blinking Kinetics. Nano Lett. 2019. 19(4):2641-2646) in view of Ramachandran et al. (WO2020/123309, on IDS dated 03/10/2023) as applied to claims 1-4, 6-8, 14-21, 32, 52-53, 56, and 113 above, and further in view of Callewaert et al., (US PGPub US20200231956A1, on IDS dated 04/20/2026).
The following is a new rejection necessitated by amendments.
Regarding claim 52, Ramachandran teaches a method of sequencing polypeptides, but does not teach the claimed method of sequencing the polypeptide.
Callewaert teaches a method for single molecule peptide sequencing comprising contacting a polypeptide one or more times with N-terminal amino acids (terminal amino acid recognition molecules), and a cleavage-inducing agent to cleave off said N-terminal amino acid (para 10) and detecting cleavage by measuring an optical, electrical or plasmonical signal, wherein a difference (pulses) in optical, electrical or plasmonical signal is indicative for cleavage of said terminal amino acid (paras 115, 118). Callewaert further teaches the polypeptide is degraded (para 153). Callewaert teaches that their method of polypeptide sequencing provides a more simple and elegant protein sequencing technology based on different physiochemical principles than mere binding affinity of reagents (para 4).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Wade and Ramachandran with Callewaert to arrive at the instantly claimed invention. The modification would have entailed selecting the method of Callewaert as the method polypeptide sequencing. Selecting an appropriate sequencing method would have been a choice determined to be routing optimization, well under the purview of one of skill in the art. One would have been motivated by the proven success and promised simplicity of the method of Callewaert. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 53, neither Wade nor Ramachandran or Callewaert teach performing the method in a single reaction vessel.
However, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Wade and Ramachandran with Callewaert to arrive at the instantly claimed invention. Regarding performing the method in a single reaction vessel, such experimental decisions are considered routine and obvious in the art and could be performed as desired for the decreased manipulation of reagents. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Conclusion
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 JESSICA GRAY whose telephone number is (571)272-0116. The examiner can normally be reached Monday-Friday 8-5 with second Fridays off.
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/JESSICA GRAY/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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