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 .
DETAILED ACTION
Pursuant to a preliminary amendment, claims 1-14, filed February 2, 2023 are currently pending in the instant application.
Response to Election/Restriction
Applicant's election with traverse of Group I, claims 1-6 and 11, directed to a method for screening for a polypeptide that acts on a target protein; and Applicant’s election with traverse of Species as follows:
Species (A): wherein the polypeptides comprise an amino acid sequence in which the predicted site is randomized in the amnio acid sequence of the ligand (claim 3), in the reply filed March 20, 2026 is acknowledged.
Response to Traversals:
The traversal of is on the grounds that: (a) the Office has not considered the relationship of the inventions of Group I-IV with respect to MPEP 806.3 (Applicant Remarks, pg. 3, entire page); (b) regarding Groups I-IV, a search of all the claims would not impose a serious burden on the examiner because the International Searching Authority searched all of the claims together (Applicant Remarks, pg. 4, second full paragraph); and (c) regarding the election of Species, Applicant makes no statement regarding the patentable distinctness of the species, but the Office has not provided any reasoning regarding this being a patentable distinction (Applicant Remarks, pg. 4, fourth and fifth full paragraphs).
Regarding (a), the Examiner did consider the contents of the claims as interpreted in light of the description. However, Applicant has not indicated or argued that the Examiner’s assessment of the claims with regard to the “special technical feature” was incorrect. The restriction is proper.
Regarding (b), it is noted that ‘search burden’ is not a criterion for restriction under 35 U.S.C. 121 and 372. Thus, the restriction requirement with respect to Groups I-IV is proper. On the international level, all written opinions are non-binding and a patent does not issue; what does issue is an international preliminary examination report (IPER), which is non-binding on the Elected States. See M.P.E.P. § 1893.03(e). Regardless, it is unclear whether the presently pending independent claims are within the Published PCT because the claims in the International Application are written in Japanese. Moreover, Applicant has not filed a certified English translation of the certified copy of the foreign priority document. The restriction requirement between Groups I-IV is proper.
Regarding (c), regarding the election of Species, Applicant has not traversed on the ground that the inventions are not patentably distinct, Applicant has not submitted evidence of record showing the inventions to be obvious variants, nor does Applicant claim on the record that this is the case. Regarding the Examiner’s reasoning, this can be found in the Requirement for Restriction/Election at pg. 4, last partial paragraph through pg. 5, first partial paragraph. The requirement of an election of Species is proper.
Claims 7, 8-10 and 12-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 5 and 11 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on February 2, 2026.
The restriction requirement is still deemed proper and is therefore made FINAL.
The claims will be examined insofar as they read on the elected species.
Therefore, claims 1-4 and 6 are under consideration to which the following grounds of rejection are applicable.
Priority
The present application filed February 2, 2023, claims the benefit of a 35 U.S.C. 371 national stage filing of International Application PCT/JP2021/028940, filed August 4, 2021, which claims the benefit Japanese Patent Application JP2020-132823, filed August 5, 2020.
Acknowledgment is made of Applicant's claim for foreign priority based on an application filed in the Japan on August 5, 2020; and of Applicant’s filing of the certified copy of Japanese Patent Application
JP2020-132823 on February 2, 2023 as required by 37 CFR 1.55.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on February 2, 2023; July 24, 2024 and December 31, 2024 have been considered. Initialed copies of the IDSs accompany this Office Action.
Claim Objections/Rejections
Claim Objections
Claim 3 is objected to because of the following informalities: Claim 3, line 4 recites the term "ODA” where an abbreviation should be spelled out in the first encounter of the claims.
Appropriate correction is required.
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 1-4 and 6 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 1 is indefinite for the recitation of the term “the expression vector” such as recited in claim 1, line 8. There is insufficient antecedent basis for the term “the expression vector” in the claim because claim 1, line 3 recites the term “a plurality of expression vectors.” The Examiner suggests that Applicant amend the claim to recite, for example, “bacterium with the plurality of expression vectors.”
Claim 3 is indefinite for the recitation of the terms “ligand,” “known membrane protein,” “predict a site,” “randomized,” and “sequence of the ligand” such as recited in claim 3, lines 4-7 because claim 3 depends from instant claim 1, wherein claim 1 does not recite the presence of any ligands, known membrane proteins, predicting sites of interaction, randomization, and/or sequences of a ligand. Thus, it is unclear what ligand and/or known membrane protein is being referred to and, thus, the metes and bounds of the claim cannot be determined.
Claim 3 is indefinite due to the use of use parentheses to comment on or qualify part of the sentences including, for example, “site(s)” such as recited in claim 3, lines 5 and 7 because it is unclear whether the limitations in parentheses are meant to be limitation in the claims, whether they are only a suggestion, an example of a preferred embodiment, a synonym, or whether they refer to something else. Accordingly, the metes and bounds of the claim are not clear.
Claim 3 is indefinite for the recitation of the term “likely” such as recited in claim 3, line 5 because the term “likely” is a relative term that renders the claim indefinite. The term “likely” is not defined by the claim, and the Specification does not provide a standard for ascertaining the requisite amount of prediction compared to some other value that qualifies as a site that is “likely” to interact with another protein, such that one of ordinary skill in the art would not be reasonably appraised of the scope of the invention and, thus, the metes and bounds of the claim cannot be determined.
Claim 3 is indefinite for the recitation of the term “(c) preparing a library comprising the polynucleotides” such as recited in claim 3, line 8 because instant claim 3 is directed to the method of “preparing the polynucleotide library in (1)” (claim 3, lines 2-3), such that the recitation of a step comprising “(c) preparing a library comprising the polynucleotides” does not actually recite the method of preparing the polynucleotide library in (1) and, thus, the metes and bounds of the claim cannot be determined.
Claim 6 is indefinite for the recitation of the term “concentrating the polynucleotide library” such as recited in claim 6, line 2 because claim 6 depends from instant claim 1, wherein claim 1 does not recite that the polynucleotide library is present in a solution, solvent, liquid, etc. Thus, is unclear what is being concentrated given that claim 1 does not recite any component from which to concentrate the polynucleotide library and, thus, the metes and bounds of the claim cannot be determined.
Claim 6 is indefinite for the recitation of the term “binds a target protein” such as recited in claim 6, line 3 because claim 6 depends from instant claim 1, wherein claim 1 does not recite that a first polynucleotide binds to anything including a target protein and, thus, the metes and bounds of the claim cannot be determined.
Claims 2 and 4 are indefinite insofar as they ultimately depend from instant claim 1.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 3 and 6 are rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 3 recites (in part): “applying an ODA analysis to a three-dimensional structure…amino acid sequence of the ligand” in lines 4-7 because claim 3 depends from instant claim 1, wherein claim 1 does not recite any ligands, known membrane proteins, predicted sites, randomization, and/or sequences of a ligand. Thus, claim 3 is an improper dependent claim for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 6 recites (in part): “further comprising a step of concentrating the polynucleotide library for the first polynucleotide encoding a polypeptide that binds to a target protein prior to performing the method” in lines 2-4 because claim 6 depends from instant claim 1, wherein claim 1 does not recite the presence of a solution, solvent, liquid, etc. that can be concentrated; and/or any binding between a polynucleotide and a target protein. Thus, claim 6 is an improper dependent claim for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-4 and 6 are rejected under 35 U.S.C. 102(a1)/102(a2) as being anticipated by Kubo et al. (hereinafter “Kubo”) (International Application WO2010104114A1, filed September 16, 2010; also JP2014207905A; and English Translation).
Regarding claim 1, Kubo teaches that the invention relates to methods of preparing polypeptide libraries and methods of using them to identify novel polypeptides (paragraph [0001]). Kubo teaches a method for preparing a polypeptide having affinity for a target protein, the method comprising the following steps (a) to (e); (a) comprising a group of expression vectors capable of expression in gram-negative bacteria; and a step of preparing a polynucleotide library, wherein each expression vector contains a plurality of polypeptides having a scaffold, and the amino acid sequences of regions involved in interaction in each polypeptide are randomized, each polynucleotide among a plurality of polynucleotides encoding each of the plurality of polypeptides is inserted, a secretory signal sequence is upstream of each polynucleotide, and a polynucleotide encoding a target protein is in tandem; (b) expressing each of the expression vectors constituting the polynucleotide library in a transformed gram-negative bacterium; wherein the target protein is expressed on the inner membrane surface and the polypeptide encoded by each polynucleotide is expressed in the periplasmic space; (c) expressing each polypeptide in the periplasmic space to the target; (d) forming spheroplasts of said transformed gram-negative bacterium to select for polypeptides that bound said target protein; (e) expressing said selected polypeptides; amplifying the polynucleotide in the transformed cell to determine the amino acid sequence of the polypeptide encoded by the polynucleotide (interpreted as the method of claim 1 including providing a polynucleotide library, a plurality of expression vectors encoding a polypeptide, transforming a gram-negative bacterium with the expression vector, contacting the polypeptide with the target protein in the periplasmic space, forming a spheroplast, and identifying the polypeptide that acts on the target protein (pg. 1, claim 1). Kubo teaches that the library can display the target protein on the inner membrane surface of E.coli, and the library using the ICK scaffold has a relatively small molecular weight and high stability, so the screening process within the perismic space is also possible, wherein it was also demonstrated that the screening technique can be used to molecularly evolve a polypeptide sequence that has a higher affinity for the target membrane protein (interpreting the gram-negative bacterium; and a target membrane protein; and identifying a polypeptide that acts on the target protein based on a measured activity such as affinity, claim 1) (paragraph [0007], lines 129-133). Kubo teaches that various signal transduction that occurs via membrane proteins, such as changes in intracellular calcium, cAMP, and arachidonic acid concentrations, and changes in electrical potential, are measured using sensitive fluorescent dyes; or alternatively, an artificial lipid membrane reconstitution system containing target membrane proteins is immobilized on a substrate, and the interaction between it and polypeptides is measured using devices such as surface plasmon resonance (SPR) and quartz crystal oscillation microbalance (QCM) (interpreted as a patch clamp technique, claim 1) (paragraph [0028], lines 689-694).
Regarding claim 2, Kubo teaches that the library can display the target protein on the inner membrane surface of E.coli, and the library using the ICK scaffold has a relatively small molecular weight and high stability, so the screening process within the perismic space is also possible, wherein it was also demonstrated that the screening technique can be used to molecularly evolve a polypeptide sequence that has a higher affinity for the target membrane protein (interpreting the gram-negative bacterium to be E. coli, claim 2) (paragraph [0007], lines 129-133).
Regarding claim 3, Kubo teaches a high-throughput screening technology that is also effective in searching for ligands for membrane proteins (interpreted as membrane protein ligands, claim 3) (paragraph [0007], lines 134-135). Kubo teaches that it has been reported from mass spectrometry and steric structure analysis that this polypeptide forms three disulfide bonds and has a physicochemically and biologically stable structure (interpreted as a 3-dimensional structure; and analysis, claim 3) (paragraph [0007], lines 98-100). Kubo teaches that the tertiary structure of A4-1 was predicted using 3D modeling software components of BioPackage, and the residues involved in loop and b-sheet formation were identified by a known hynantoxin (HnTx4) (Figure 3) (interpreting BioPackage as an ODA analysis to a 3-dimensional structure analysis of a ligand for a known protein, claim 3) (paragraph [0013], lines 357-359; and Figure 3). Kubo teaches that in the polypeptide library of the present invention, the amino acid sequences of the loop I, II and III regions and part of the tail region of the ICK scaffold are randomized and have affinity with the target protein; and are used for screening high polypeptides (interpreted as randomized predicted site in the amino acid sequence of the ligand, claim 3) (paragraph [0014], lines 372-374). Kubo teaches that in a randomized polypeptide, all possible amino acid residues at a given position can be present with equal or unequal probability, and only two or more of the particular amino acid residues selected for a given position can be present (interpreted as randomized polypeptides, claim 3) (paragraph [0014], lines 390-392). Kubo teaches that Figure 1 shows the regions predicted to form loops and the amino acid residues around them were randomized (interpreted as preparing polypeptide in which the predicted site is randomized; and forming a polypeptide library, claim 3) (paragraph [0031], lines 751-752; and Figure 1).
Regarding claim 4, Kubo teaches that the polypeptide comprises the amino acid sequence of any one of SEQ ID NOS: 3 to 14, which has a high affinity for the m2 receptor (interpreting the m2 receptor as a membrane receptor, claim 4) (paragraph [0008], lines 276-277). Kubo teaches that as the target protein, not only calcium channels, which are the original target, but also various ion channels, receptors, enzymes, and other natural and non-natural compounds can be selected as targets (interpreted as including ion channel and receptors as target proteins, claim 4) (paragraph [0014], lines 375-377).
Regarding claim 6, Kubo teaches that it is possible to produce a second polypeptide library consisting of a group of a plurality of polypeptides, some of which are identical in amino acid sequence to those of the polypeptides selected in the previous round and differ in the remaining amino acids, wherein this second polypeptide library can then be used to select polypeptides that bind the target, followed by multiple rounds of selection and further randomization of the library, and so on, such that it becomes possible to introduce further mutations into the target-binding polypeptides to promote artificial molecular evolution; and that each round, amplification, transformation (or transcription/translation), and selection are sequentially repeated, such that after repeating selection/concentration for 5 or more rounds, peptide sequences converge into about 10 groups (interpreted as concentrating the polypeptide library for the first polynucleotide encoding a polypeptide that binds to a target protein prior to performing the method, claim 6) (paragraph [0025], lines 624-630 and 639-641).
Kubo meets all the limitations of the claims and, therefore, anticipates the claimed invention.
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 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 may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claims 1-4 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Kubo et al. (hereinafter “Kubo”) (International Application WO2010104114A1, filed September 16, 2010; also JP2014207905A; and English Translation) in view of Fernandez-Recio et. al. (hereinafter “Fernandez-Recio”) (Proteins: Structure, Function, and Bioinformatics, 2005, 58, 134-143).
The teachings of Kubo as applied to claims 1-4 and 6 are described supra.
Kubo does not specifically use the term optimal docking area (claim 3, in part).
Regarding claim 3, Fernandez-Recio teaches Optimal Docking Area (ODA), a new fast and accurate method of analyzing a protein surface in search of areas with favorable energy change when buried upon protein–protein association, wherein the method identifies continuous surface patches with optimal docking desolvation energy based on atomic solvation parameters adjusted for protein–protein docking, wherein the procedure has been validated on the unbound structures of a total of 66 non-homologous proteins involved in non-obligate protein–protein hetero-complexes of known structure, such that optimal docking areas with significant low docking surface energy were found in around half of the proteins, such that the ‘ODA hot spots’ detected in X-ray unbound structures were correctly located in the known protein–protein binding sites in 80% of the cases (interpreted as ODA analysis, claim 3) (Abstract).
“It is prima facie obvious to combine prior art elements according to known methods to yield predictable results; the court held that, "…a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1395 (2007); Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969); Great Atlantic & P. Tea Co. v. Supermarket Equipment Corp., 340 U.S. 147, 152, 87 USPQ 303, 306 (1950)”. Therefore, in view of the benefits of understanding energetics and mechanisms of protein-protein associations as exemplified by Fernandez-Recio, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to modify the method for preparing polypeptides having affinity to a target protein using a library of polypeptides comprised of a group of expression vectors, and expressing each expression vector comprising the polynucleotide library in a transformed gram-negative bacterium to ultimately determine the polypeptide which the polynucleotide encodes as disclosed by Kubo, to include the ODA analysis method including identifying ODA hot spots that correspond with known protein-protein interfaces as taught by Fernandez-Recio with a reasonable expectation of success in identifying protein-protein binding interfaces by identifying continuous surface patches with optimal docking desolvation energy; and/or in predicting protein-protein interaction sties including in regions of each polypeptide involved in protein binding interactions.
Thus, in view of the foregoing, the claimed invention, as a whole, would have been obvious to one of ordinary skill in the art at the time the invention was made. Therefore, the claims are properly rejected under 35 USC §103 as obvious over the art.
Conclusion
Claims 1-4 and 6 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M BUNKER whose telephone number is (313) 446-4833. The examiner can normally be reached on Monday-Friday (6am-2:30pm).
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/AMY M BUNKER/Primary Examiner, Art Unit 1684
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