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
This application is a 371 of PCT/GB2022/052751.
The amendment filed on November 12, 2024 has been entered.
Status of Claims
Claims 1-2, 4, 7, 10, 13, 15, 17, 20-21, 23-24, 27, 30, 36, 40, 44, 46-48, and 54 are pending.
Claims 1-2, 4, 7, 10, 13, 15, 17, 20-21, 23-24, 27, 30, 36, 40, 44, 46-48, and 54 are under examination.
Multiple dependent claim(s), improper
Claims 44 and 46 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim should not reference two sets of claims to different features. Claim 44 depends from claim 1 (product) and claim 36 (method). Claim 46 depends from claim 44. See MPEP § 608.01(n). Accordingly, the claims 44 and 46 have not been further treated on the merits.
Claim 54 is objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim should not reference two sets of claims to different features. Claim 54 depends from claim 1 (product) and claim 47(method). See MPEP § 608.01(n). Accordingly, the claim 54 has not been further treated on the merits.
Response to Amendments/Arguments
Nucleotide and/or Amino Acid Sequence Disclosures - Drawings
Specific deficiency
Applicant’s arguments, see page 10 of the Remarks, filed June 12, 2026, with respect to the Drawings have been fully considered and are persuasive. Sequence indenters have been added to the specification. Therefore, the objection of the Drawings has been withdrawn.
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.
Withdrawn Rejections
Applicant’s arguments, see pages 10-11 of the Remarks, filed June 12, 2026, with respect to claim 2 have been fully considered and are persuasive. Claim 2 has been amended to recite one range of error rate. Therefore, the rejection of claim 2 under 35 U.S.C. 112(b) has been withdrawn.
Applicant’s arguments, see pages 10-11 of the Remarks, filed June 12, 2026, with respect to claims 4, 15, and 17 have been fully considered and are persuasive. Claims 4, 15, and 17 been amended to recite one range of sequence identity. Therefore, the rejection of claims 4, 15, and 17 under 35 U.S.C. 112(b) has been withdrawn.
Applicant’s arguments, see pages 10-11 of the Remarks, filed June 12, 2026, with respect to claims 2, 7, 21, 27, 40, 44, and 48 and claim 30 depending therefrom have been fully considered and are persuasive. Claims 2, 7, 21, 27, 40, 44, and 48 have been amended to delete the phrase “preferably”. Therefore, the rejection of claims 2, 7, 21, 27, 40, 44, and 48 and claim 30 depending therefrom under 35 U.S.C. 112(b) has been withdrawn.
New Rejection
Claims 1 and 13 and claims 2, 4, 7, 10, 15, 17, 20-21, 23-24, 27, 30, 36, 40, and 47-48, are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1 and 13 recite the phrase “DNA polymerase..comprising the amino acid sequence of SEQ ID NO:1…, wherein the amino acid sequence..comprises a modification at or corresponding to potion L903, D390 and E392…”. The metes and bounds of the phrase in the context of the claims are not clear. It is unclear how a polypeptide can comprise the amino acid sequence of SEQ ID NO:1 and also have amino acid modifications. A polypeptide either has the amino acid sequence of a given sequence identifier or it does not. Appropriate correction is requested
Claim Rejections - 35 USC § 112(d)
Applicant’s arguments, see page 11 of the Remarks, filed June 12, 2026, with respect to claim 17 have been fully considered and are persuasive. Claim 17 has been amended to recite “the nucleic acid sequence of SEQ ID NO:4”, which properly depends from claim 1. Therefore, the rejection of claim 17 under 35 U.S.C. 112(d) has been withdrawn.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-2, 4, 7, 10, 13, 15, 17, 20-21, 23-24, 27, 30, 36, 40, and 47-48 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP 2111.01 states that ''[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow.''. Claims 1-2, 4, 7, 10, 13, 15, 17, 20-21, and 24 encompass any organellar DNA polymerase having at least 35% sequence identity to SEQ ID NO:1 or 2, organellar DNA polymerase comprising the amino acid sequence of SEQ ID NO:1 or 2, encoded by a polynucleotide comprising the nucleic acid sequence of SEQ ID NO:4, or encoded by a polynucleotide having at least 35% sequence identity to SEQ ID NO:1 or 4, wherein the organellar DNA polymerase has L903X, D390X, and E392 amino acid substitutions. Claims 27, 36, 40, 47, and 48 encompass a method of modifying a plant or any plant part thereof, method of modifying organelle DNA, or a method of producing a plant or any plant part thereof having homoplastic modified organelle DNA using the DNA polymerase described above. Claim 30 encompass any modified plant or modified organelle produced by the above methods. Therefore, the claims are drawn to (A) a genus of DNA polymerase having unknown structure except not having a Leu, Asp, and Glu residues at the positions corresponding to 903, 390 and 392, respectively, of SEQ ID NO:1 or 2, (B) a method of modifying a genus of plant or any plant part thereof, method of modifying organelle DNA, or a method of producing any plant or any plant part thereof having homoplastic modified organelle DNA using the genus of DNA polymerase described of (A) or a genus of any error-prone DNA polymerase, and (C) genus of modified plants or genus of plant parts having unknown structure and genus of modified organelles having unknown structure.
MPEP 2163 I. states that to “satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention.
MPEP 2163. II.A.3.(a) sates that “Possession may be shown in many ways. For example, possession may be shown by describing an actual reduction to practice of the claimed invention. Possession may also be shown by a clear depiction of the invention in detailed drawings or in structural chemical formulas which permit a person skilled in the art to clearly recognize that inventor had possession of the claimed invention. An adequate written description of the invention may be shown by any description of sufficient, relevant, identifying characteristics so long as a person skilled in the art would recognize that the inventor had possession of the claimed invention.
According to MPEP 2163.II.A.3.(a).ii), “Satisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus…Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’"
The recitation of “organellar DNA polymerase”, “error-prone DNA polymerase, “modified plant or part thereof”, “modified organelle”, and “plant having homoplasmic modified organelle DNA” fails to provide a sufficient description of the genus of the polypeptides, polynucleotides, plant or part thereof, and organelle as it merely describes the functional features of the genus without providing any definition of the structural features of the species within the genus. The specification does not specifically define any of the species that fall within the genus. The specification does not define any structural features commonly possessed by members of the genus that distinguish them from others. One skilled in the art therefore cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genus.
Nicotina tobacum DNA polymerase was known in the art. Ono (NtPolI-like1 and NtPolI-like2, bacterial DNA polymerase I homologs isolated from BY-2 cultured tobacco cells, encode DNA polymerases engaged in DNA replication in both plastids and mitochondria. Plant Cell Physiol. 2007 Dec;48(12):1679-92– form PTO-892) discloses a Nicotina tobacum DNA polymerase that is identical to the DNA polymerase of SEQ ID NO:1 of the instant application except for one amino acid (Fig. 1 and see the sequence alignment below). However, any DNA polymerase having unknown structure except not having Leu, Asp, and Glu residues at the positions corresponding to 903, 390 and 392, respectively, of SEQ ID NO:1 or 2, wherein the DNA polymerase has organellar DNA polymerase activity, the error rates recited in claim 2, ability to modify any plant or part thereof or any organelle and producing any plant or part thereof or any organelle was not known in the art.
Fransceus (J Ind Microbiol Biotechnol. 2017 May;44(4-5):687-695. – cited previously on form PTO-892) reviews protein engineering techniques, such as random mutagenesis and recombination, directed evolution and iterative or combinatory saturation “hotspots”. Fransceus states that “a recurring problem, however, is choosing which amino acid positions should be targeted. Answering this question is not an easy feat and requires substantial insight in the relationship between an enzyme’s sequence or structure and its properties.” Sanavia (Computational and Structural Biotechnology Journal, Volume 18, 2020, Pages 1968-1979. – cited previously on form PTO-892) discloses challenges in the prediction of protein stability in the occurrence of multiple mutations. “Multiple-point mutations are common variations of the protein sequence that may be needed in protein engineering when a single-point mutation is not enough to yield the desired stability change. Dealing with multiple-site variations adds another level of complexity beyond the prediction of the effect of a single variant on protein stability, since it requires the learning of many types of combinatorial effects”.
The specification is limited to the description of an error-prone organellar DNA polymerase having the amino acid sequence of SEQ ID NO:2 (mutant of SEQ ID NO:1 consisting of D390A/E392AL903F), method of modifying a tobacco with said polymerase, and tobacco comprising said polymerase. While MPEP 2163 acknowledges that in certain situations “one species adequately supports a genus,” it also acknowledges that “[f]or inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus.” In view of the widely variant species encompassed by the genus, the above-described example is not enough and does not constitute a representative number of species to describe the whole genus. Therefore, the specification fails to describe a representative species of the claimed genus.
Further, one of skill in the art could identify polypeptides having at least 35% sequence identity to SEQ ID NO:1 or 2. However, there is no teaching regarding which 65% of the amino acids can vary from SEQ ID NO:1 or 2 except at position L903, D390, and E392 and result in polypeptide having organellar DNA polymerase activity, the error rates recited in claim 2, ability to modify any plant or part thereof or any organelle and producing any plant or part thereof or any organelle. An important consideration is that structure is not necessarily a reliable indicator of function. In the instant case, there is no disclosure relating similarity of structure to conservation of function. Conservation of structure is not necessarily a surrogate for conservation of function. Since the claimed invention is that of an enzyme, and there is no disclosure of the domains responsible for organellar DNA polymerase activity, the error rates recited in claim 2, ability to modify any plant or part thereof or any organelle and producing any plant or part thereof or any organelle the absence of information may be persuasive that those of skill in the art would not take the disclosure as generic.
While general knowledge in the art may have allowed one of skill in the art to identify other polypeptides expected to have the same or similar tertiary structure, there was no general knowledge in the art about polypeptides having at least 35% sequence identity to SEQ ID NO:1 or 2 and having organellar DNA polymerase activity, the error rates recited in claim 2, ability to modify any plant or part thereof or any organelle and producing any plant or part thereof or any organelle.
Given this lack of description of the representative species encompassed by the genus of the claims, the specification fails to sufficiently describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize that applicants were in possession of the inventions of claims 1-2, 4, 7, 10, 13, 15, 17, 20-21, 23-24, 27, 30, 36, 40, and 47-48.
Applicant's arguments filed June 12, 2026 have been fully considered but they are not persuasive.
Applicant argues that since the claims 1, 13, 15, and 17 have been amended to recite “the amino acid sequence of SEQ ID NO” and claim 4 has been amended to recite “an amino acid sequence having at least 35%..identity to the amino acid sequence of SEQ ID NO:”, the claims meet the written description requirement.
This is not found persuasive.
The claims are directed to any organellar DNA polymerase having at least 35% sequence identity to SEQ ID NO:1 or 2, organellar DNA polymerase comprising the amino acid sequence of SEQ ID NO:1 or 2, encoded by a polynucleotide comprising the nucleic acid sequence of SEQ ID NO:4, or encoded by a polynucleotide having at least 35% sequence identity to SEQ ID NO:1 or 4, wherein the organellar DNA polymerase has L903X, D390X, and E392 amino acid substitutions and any other amino acid modifications. Therefore, the claims are drawn to a genus of DNA polymerase having unknown structure except not having a Leu, Asp, and Glu residues at the positions corresponding to 903, 390 and 392, respectively, of SEQ ID NO:1 or 2. The specification is limited to the description of an error-prone organellar DNA polymerase having the amino acid sequence of SEQ ID NO:2 (mutant of SEQ ID NO:1 consisting of D390A/E392AL903F), method of modifying a tobacco with said polymerase, and tobacco comprising said polymerase. However, there is no teaching regarding which amino acids can vary in the organellar DNA polymerase having 35-100% sequence identity to the amino acid sequence of SEQ ID NO:1or 2, except at position L903, D390, and E392, and result in polypeptide having organellar DNA polymerase activity, the error rates recited in claim 2, ability to modify any plant or part thereof or any organelle and producing any plant or part thereof or any organelle. Therefore, the specification fails to describe a representative species of the claimed genus.
Applicant argues that the claims meet the written description requirement because (1) the specification teaches a wide range of representative species of a genus of sequences having at least 35% sequence identity to SEQ ID NO:1 that perform the same DNA polymerase function (pages 20, 22, Figures 1 and 24, and page 66), (2) the claimed modifications are readily identifiable in the claimed genus of DNA polymerases and the modification of position corresponding to SEQ ID NO:1 is possible in part due to the highly conserved nature of these functional domains (pages 28-29, Figure 2A, pages 70-71), and (3) it is described on page 71, first paragraph, and shown in Figure 2B, that a highly conserved eight amino acid sequence DYSQIELR in motif A of the polymerization domain in the distant E. coli DNA Pol I is aligned with the corresponding region of NtPOPtom. It is described that that substitutions at isoleucine 709 of E. coli DNA Pol I within this DYSQIELR motif still gave rise to an efficient mutator (high error rate) DNA polymerase, and (4) Applicant submits herewith an alignment between SEQ ID NO: 1 and a modified organellar DNA polymerase from Chlamydomonas reinhardtii into which D390A, E392A and L903F modifications have been introduced (submitted here with as Exhibit), demonstrating that these polymerases have as little as 28.6% identity yet the modifications recited in claim 1 can be readily introduced based on the written description.
This is not found persuasive.
(1)-(2) The claims are not limited to organellar DNA polymerase consisting of amino acid modifications at the positions corresponding to L903, D390, and E392 of SEQ ID NO:1 of the instant application. Instead, the claims encompass any mutant of the organellar DNA polymerase having the amino acid sequence of SEQ ID NO:1 or having at least 35% sequence identity to SEQ ID NO:1 (allowing for 749 amino acid differences to SEQ ID NO:1), wherein the mutant comprises modifications at the positions corresponding to L903, D390, and E392 of SEQ ID NO:1 and any other number of amino acid modifications. There is no teaching regarding which amino acids can vary in the organellar DNA polymerase having 35-100% sequence identity to the amino acid sequence of SEQ ID NO:1or 2, except at position L903, D390, and E392, and result in polypeptide having organellar DNA polymerase activity, the error rates recited in claim 2, ability to modify any plant or part thereof or any organelle and producing any plant or part thereof or any organelle. As discussed in the rejection, Sanavia discloses challenges in the prediction of protein stability in the occurrence of multiple mutations. “Multiple-point mutations are common variations of the protein sequence that may be needed in protein engineering when a single-point mutation is not enough to yield the desired stability change. Dealing with multiple-site variations adds another level of complexity beyond the prediction of the effect of a single variant on protein stability, since it requires the learning of many types of combinatorial effects”.
Further, although the specification discloses exemplary organellar DNA polymerases which can be modified, a “laundry list” disclosure of every possible moiety does not necessarily constitute a written description of every species in a genus because it would not “reasonably lead” those skilled in the art to any particular species, see Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 USPQ2d 1895, 1905 (Fed. Cir. 1996) or MPEP 2163. While the exemplary organellar DNA polymerases were known in the art, this knowledge alone would not allow one level of skill in the art to immediately envisage the claimed genus organellar DNA polymerase. Therefore, the level of skill and knowledge in the art is such that one of ordinary skill would not be able to identify without further testing which organellar DNA polymerase to modify to arrive at the claimed invention.
(3) The DYSQIELR in motif is limited to E. coli Poll and NtPOP. The instant claims are directed to a wide genus of organellar DNA polymerases.
(4) The sequence alignment of Exhibit is illegible and Applicant has not provided the amino acid sequence of the C. reinhardtii POP. Further, the claims are not limited organellar DNA polymerase consisting of amino acid modifications at the positions corresponding to L903, D390, and E392 of SEQ ID NO:1 of the instant application. Instead, the claims are drawn to a genus of DNA polymerase having unknown structure except not having a Leu, Asp, and Glu residues at the positions corresponding to 903, 390 and 392, respectively, of SEQ ID NO:1 or 2. There is no teaching regarding which amino acids can vary in the organellar DNA polymerase having 35-100% sequence identity to the amino acid sequence of SEQ ID NO:1or 2, except at position L903, D390, and E392, and result in polypeptide having organellar DNA polymerase activity, the error rates recited in claim 2, ability to modify any plant or part thereof or any organelle and producing any plant or part thereof or any organelle. Therefore, the specification fails to describe a representative species of the claimed genus.
Hence the rejection has been maintained.
Claims 1-2, 4, 7, 10, 13, 15, 17, 20-21, 23-24, 27, 30, 36, 40, and 47-48 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for an error-prone organellar DNA polymerase having the amino acid sequence of SEQ ID NO:2 (mutant of SEQ ID NO:1 consisting of D390A/E392AL903F), method of modifying a tobacco with said polymerase, and tobacco comprising said polymerase, does not reasonably provide enablement for (A) any DNA polymerase having unknown structure except not having Leu, Asp, and Glu residues at the positions corresponding to 903, 390 and 392, respectively, of SEQ ID NO:1 or 2, (B) a method of modifying a any plant or any plant part thereof, method of modifying organelle DNA, or a method of producing any plant or any plant part thereof having homoplastic modified organelle DNA using any DNA polymerase described of (A) or any error-prone DNA polymerase, and (C) any modified plants or genus of plant parts having unknown structure and any modified organelle having unknown structure.
. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.
The breadth of the claims.
MPEP 2111.01 states that ''[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow.''. Claims 1-2, 4, 7, 10, 13, 15, 17, 20-21, and 24 encompass any organellar DNA polymerase having at least 35% sequence identity to SEQ ID NO:1 or 2, organellar DNA polymerase comprising the amino acid sequence of SEQ ID NO:1 or 2, encoded by a polynucleotide comprising the nucleic acid sequence of SEQ ID NO:4, or encoded by a polynucleotide having at least 35% sequence identity to SEQ ID NO:1 or 4, wherein the organellar DNA polymerase has L903X, D390X, and E392 amino acid substitutions. Claims 27, 36, 40, 47, and 48 encompass a method of modifying a plant or any plant part thereof, method of modifying organelle DNA, or a method of producing a plant or any plant part thereof having homoplastic modified organelle DNA using the DNA polymerase described above. Claim 30 encompass any modified plant or modified organelle produced by the above methods. Therefore, the claims are drawn to (A) any DNA polymerase having unknown structure except not having Leu, Asp, and Glu residues at the positions corresponding to 903, 390 and 392, respectively, of SEQ ID NO:1 or 2, (B) a method of modifying a any plant or any plant part thereof, method of modifying organelle DNA, or a method of producing any plant or any plant part thereof having homoplastic modified organelle DNA using any DNA polymerase described of (A) or any error-prone DNA polymerase, and (C) any modified plants or genus of plant parts having unknown structure and any modified organelle having unknown structure.
The claims are not commensurate with the enablement provided by the disclosure with regard to the extremely large number of organelle DNA polymerases, error-prone DNA polymerases, plant or parts thereof, or organelles. In the instant case, the specification is limited to an error-prone organellar DNA polymerase having the amino acid sequence of SEQ ID NO:2 (mutant of SEQ ID NO:1 consisting of D390A/E392AL903F), method of modifying a tobacco with said polymerase, and tobacco comprising said polymerase.
The quantity of experimentation required to practice the claimed invention based on the teachings of the specification.
While enzyme isolation techniques, recombinant and mutagenesis techniques were known in the art at the time of the invention, e.g. mutagenesis, and it is routine in the art to screen for variants comprising multiple substitutions or multiple modifications as encompassed by the instant claims, the specific amino acid positions within the protein's sequence where amino acid modifications can be made with a reasonable expectation of success in obtaining the desired activity/utility are limited in any protein and the result of such modifications is unpredictable. In addition, one skilled in the art would expect any tolerance to modification for a given protein to diminish with each further and additional modification, e.g. multiple substitutions.
In the absence of: (a) rational and predictable scheme for making any polypeptides having at least 35% sequence identity to SEQ ID NO:1 or 2 or any fragments thereof, wherein the polypeptides have organellar DNA polymerase activity, the error rates recited in claim 2, ability to modify any plant or part thereof or any organelle and producing any plant or part thereof or any organelle, and (b) a correlation between structure and the function of having organellar DNA polymerase activity, the error rates recited in claim 2, ability to modify any plant or part thereof or any organelle and producing any plant or part thereof or any organelle, the specification provides insufficient guidance as to which of the essentially infinite possible choices is likely to be successful. One of skill in the art would have to test these infinite possible polypeptides to determine which polypeptides have organellar DNA polymerase activity, the error rates recited in claim 2, ability to modify any plant or part thereof or any organelle and producing any plant or part thereof or any organelle. While enablement is not precluded by the necessity for routine screening, if a large amount of screening is required, as is the case herein, the specification must provide a reasonable amount of guidance which respect to the direction in which the experimentation should proceed so that a reasonable number of species can be selected for testing. In view of the fact that such guidance has not been provided in the instant specification, it would require undue experimentation to enable the full scope of the claims.
The state of prior art, the relative skill of those in the art, and predictability or unpredictability of the art.
Since the amino acid sequence of the polypeptide determines its structural and functional properties, predictability of which changes can be tolerated in a protein's amino acid sequence and obtain the desired activity requires a knowledge of and guidance with regard to which amino acids in the protein's sequence, if any, are tolerant of modification and which are conserved (i.e. expectedly intolerant to modification), and detailed knowledge of the ways in which the proteins' structure relates to its function. In the instant case, neither the specification or the art provide a correlation between structure and activity such that one of skill in the art can envision the structure of any polypeptides having galactose oxidase activity or predict said function of a polypeptide from its primary structure. In addition, the art does not provide any teaching or guidance as to (1) which amino acids within the polypeptide of SEQ ID NO:1 or 2 or any fragments thereof (other than L903, D390, and E392) that can be modified and which ones are conserved such that one of skill in the art can make the recited polypeptides having organellar DNA polymerase activity, the error rates recited in claim 2, ability to modify any plant or part thereof or any organelle and producing any plant or part thereof or any organelle, (2) which segments of the polypeptide of SEQ ID NO:1 or 2 that are essential for polypeptides having organellar DNA polymerase activity, the error rates recited in claim 2, ability to modify any plant or part thereof or any organelle and producing any plant or part thereof or any organelle, and (3) the general tolerance of the polypeptide of SEQ ID NO:1 or 2 to structural modifications and the extent of such tolerance. The art clearly teaches that changes in a protein's amino acid sequence to obtain the desired activity without any guidance/knowledge as to which amino acids in a protein are required for that activity is highly unpredictable. At the time of the invention there was a high level of unpredictability associated with altering a polypeptide sequence with an expectation that the polypeptide will maintain the desired activity. For example, Studer (Residue mutations and their impact on protein structure and function: detecting beneficial and pathogenic changes. Biochem. J. (2013) 449, 581–594. – form PTO-1449) teach that (1) protein engineers are frequently surprised by the range of effects caused by single mutations that they hoped would change only one specific and simple property in enzymes, (2) the often surprising results obtained by experiments where single mutations are made reveal how little is known about the rules of protein stability, and (3) the difficulties in designing de novo stable proteins with specific functions.
Nicotina tobacum DNA polymerase was known in the art. Ono (NtPolI-like1 and NtPolI-like2, bacterial DNA polymerase I homologs isolated from BY-2 cultured tobacco cells, encode DNA polymerases engaged in DNA replication in both plastids and mitochondria. Plant Cell Physiol. 2007 Dec;48(12):1679-92– cited previously on form PTO-892) discloses a Nicotina tobacum DNA polymerase that is identical to the DNA polymerase of SEQ ID NO:1 of the instant application except for one amino acid (Fig. 1 and see the sequence alignment below). However, any DNA polymerase having unknown structure except not having a Leu, Asp, and Glu residues at the position corresponding to 903, 390 and 392, respectively, of SEQ ID NO:1 or 2, wherein the DNA polymerase has organellar DNA polymerase activity, the error rates recited in claim 2, ability to modify any plant or part thereof or any organelle and producing any plant or part thereof or any organelle was not known in the art.
Fransceus (J Ind Microbiol Biotechnol. 2017 May;44(4-5):687-695. – cited previously on form PTO-892) reviews protein engineering techniques, such as random mutagenesis and recombination, directed evolution and iterative or combinatory saturation “hotspots”. Fransceus states that “a recurring problem, however, is choosing which amino acid positions should be targeted. Answering this question is not an easy feat and requires substantial insight in the relationship between an enzyme’s sequence or structure and its properties.” Sanavia (Computational and Structural Biotechnology Journal, Volume 18, 2020, Pages 1968-1979. – cited previously on form PTO-892) discloses challenges in the prediction of protein stability in the occurrence of multiple mutations. “Multiple-point mutations are common variations of the protein sequence that may be needed in protein engineering when a single-point mutation is not enough to yield the desired stability change. Dealing with multiple-site variations adds another level of complexity beyond the prediction of the effect of a single variant on protein stability, since it requires the learning of many types of combinatorial effects”.
The amount of direction or guidance presented and the existence of working examples.
The specification is limited to an error-prone organellar DNA polymerase having the amino acid sequence of SEQ ID NO:2 (mutant of SEQ ID NO:1 consisting of D390A/E392AL903F), method of modifying a tobacco with said polymerase, and tobacco comprising said polymerase. However, the speciation fails to provide any information as to (1) specific substrates associated with any polypeptide having at least 35% sequence identity to SEQ ID NO: 1 or 2 or any fragments thereof or (2) structural elements required in a polypeptide having at least 35% sequence identity to SEQ ID NO: 2 or any fragments thereof having organellar DNA polymerase activity, the error rates recited in claim 2, ability to modify any plant or part thereof or any organelle and producing any plant or part thereof or any organelle. No correlation between structure and function of having organellar DNA polymerase activity, the error rates recited in claim 2, ability to modify any plant or part thereof or any organelle and producing any plant or part thereof or any organelle has been presented.
Thus, in view of the overly broad scope of the claims, the lack of guidance and working examples provided in the specification, the high level of unpredictability of the prior art in regard to structural changes and their effect on function and the lack of knowledge about a correlation between structure and function, an undue experimentation would be necessary one having ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of polypeptides having the desired biological characteristics recited in the claims are unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
Applicant's arguments filed June 12, 2026 have been fully considered but they are not persuasive.
Applicant argues that since the claims have been amended to require a modification L903, D390 and E392, the skilled person would appreciate that substitution with a functionally equivalent amino acids to F, A and A at positions L903, D390 and E392, respectively, would similarly enhance error rates.
This is not found persuasive.
The claims are directed to any DNA polymerase having unknown structure except not having Leu, Asp, and Glu residues at the positions corresponding to 903, 390 and 392, respectively, of SEQ ID NO:1 or 2. As discussed in the rejection, Fransceus states that “a recurring problem, however, is choosing which amino acid positions should be targeted. Answering this question is not an easy feat and requires substantial insight in the relationship between an enzyme’s sequence or structure and its properties.” In the absence of: (a) rational and predictable scheme for making any polypeptides having at least 35-100% sequence identity to SEQ ID NO:1 or 2 or any fragments thereof, wherein the polypeptides have organellar DNA polymerase activity, the error rates recited in claim 2, ability to modify any plant or part thereof or any organelle and producing any plant or part thereof or any organelle, and (b) a correlation between structure and the function of having organellar DNA polymerase activity, the error rates recited in claim 2, ability to modify any plant or part thereof or any organelle and producing any plant or part thereof or any organelle, the specification provides insufficient guidance as to which of the essentially infinite possible choices is likely to be successful. Without specific guidance, those skilled in the art will be subjected to undue experimentation of making and testing each of the enormously large number of polypeptides having organellar DNA polymerase activity, the error rates recited in claim 2, ability to modify any plant or part thereof or any organelle and producing any plant or part thereof or any organelle. Therefore, it would require undue experimentation of the skilled artisan to practice the claimed invention.
Hence the rejection has been maintained.
Claim Rejections - 35 USC § 102
Applicant’s arguments, see page 14 of the Remarks, filed June 12, 2026, with respect to claims 44, 46, and 54 have been fully considered. Claims 44, 46, and 54 are improper multiple dependent claims and have not been further treated on the merits, see above. Therefore, the rejection of claims 44, 46, and 54 under 35 U.S.C. 102(a)(1) as being anticipated by McBride (US Patent No. 5,925,806 - form PTO-892) has been withdrawn.
Applicant’s arguments, see page 14 of the Remarks, filed June 12, 2026, with respect to claims 44, 46, and 54 have been fully considered. Claims 44, 46, and 54 are improper multiple dependent claims and have not been further treated on the merits, see above. Therefore, the rejection of claims 44, 46, and 54 under 35 U.S.C. 102(a)(1) as being anticipated by Svab (High-frequency plastid transformation in tobacco by selection for a chimeric aadA gene. Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):913-7. - form PTO-892) has been withdrawn.
Claim Rejections - 35 USC § 103
Applicant’s arguments, see page 15 of the Remarks, filed June 12, 2026, with respect to claims 47 and 54 have been fully considered. Claim 54 is an improper multiple dependent claim and has not been further treated on the merits, see above. Claim 47 has been amended to recite introducing the organellar DNA polymerase of claim 1, which is not taught by Svab (High-frequency plastid transformation in tobacco by selection for a chimeric aadA gene. Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):913-7. - form PTO-892) and Das (IN 201402811. Published on March 18, 2018. Abstract – form PTO-892). Therefore, the rejection of claims 47 and 54 under 35 U.S.C. 103 as being as being unpatentable over Svab and Das has been withdrawn.
Other Relevant Art
Ji (Construction of a highly error-prone DNA polymerase for developing organelle mutation systems. Nucleic Acids Res. 2020 Dec 2;48(21):11868-11879. Published online on November 2, 2020 – form PTO-1449) discloses an error-prone organellar tobacco DNA polymerase having an L903F amino acid substitution and methods of modifying a plant and organelle DNA with said polymerase. However, Ji is not available as prior art because the 102(b)(1)(A) exception applies. The publication date of Ji is within the 1 year grace period and the authors of the reference of Ji are identical to the inventors of the instant application.
Conclusion
Claims 1-2, 4, 7, 10, 13, 15, 17, 20-21, 23-24, 27, 30, 36, 40, 44, 46-48, and 54 are pending.
Claims 1-2, 4, 7, 10, 13, 15, 17, 20-21, 23-24, 27, 30, 36, 40, and 47-48 are rejected.
Claims 44, 46, and 54 are objected.
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 YONG D PAK whose telephone number is (571)272-0935. The examiner can normally be reached M-Th: 5:30 am - 3:30 pm.
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/YONG D PAK/Primary Examiner, Art Unit 1652
Sequence alignment between the organellar DNA polymerase of SEQ ID NO:1 of the instant application (“Qy”) and the DNA polymerase of Ono (“Db”)
Q3LHT0_TOBAC
ID Q3LHT0_TOBAC Unreviewed; 1152 AA.
AC Q3LHT0;
DT 08-NOV-2005, integrated into UniProtKB/TrEMBL.
DT 08-NOV-2005, sequence version 1.
DT 08-OCT-2025, entry version 63.
DE RecName: Full=DNA-directed DNA polymerase {ECO:0000256|ARBA:ARBA00012417};
DE EC=2.7.7.7 {ECO:0000256|ARBA:ARBA00012417};
DE AltName: Full=DNA polymerase PolI-like B {ECO:0000256|ARBA:ARBA00079253};
GN Name=NtpolI-like1 {ECO:0000313|EMBL:BAE45850.1};
OS Nicotiana tabacum (Common tobacco).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; lamiids; Solanales; Solanaceae; Nicotianoideae; Nicotianeae;
OC Nicotiana.
OX NCBI_TaxID=4097 {ECO:0000313|EMBL:BAE45850.1};
RN [1] {ECO:0000313|EMBL:BAE45850.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=17942449; DOI=10.1093/pcp/pcm140;
RA Ono Y., Sakai A., Takechi K., Takio S., Takusagawa M., Takano H.;
RT "NtPolI-like1 and NtPolI-like2, bacterial DNA polymerase I homologs
RT isolated from BY-2 cultured tobacco cells, encode DNA polymerases engaged
RT in DNA replication in both plastids and mitochondria.";
RL Plant Cell Physiol. 48:1679-1692(2007).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) +
CC diphosphate; Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-
CC COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112;
CC EC=2.7.7.7; Evidence={ECO:0000256|ARBA:ARBA00049244};
CC -!- SIMILARITY: Belongs to the DNA polymerase type-A family.
CC {ECO:0000256|ARBA:ARBA00007705}.
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DR EMBL; AB174898; BAE45850.1; -; mRNA.
DR AlphaFoldDB; Q3LHT0; -.
DR SMR; Q3LHT0; -.
DR GO; GO:0009507; C:chloroplast; IEA:UniProtKB-ARBA.
DR GO; GO:0005739; C:mitochondrion; IEA:GOC.
DR GO; GO:0008408; F:3'-5' exonuclease activity; IEA:InterPro.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003887; F:DNA-directed DNA polymerase activity; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0006264; P:mitochondrial DNA replication; IEA:UniProtKB-ARBA.
DR GO; GO:0033259; P:plastid DNA replication; IEA:UniProtKB-ARBA.
DR CDD; cd08640; DNA_pol_A_plastid_like; 1.
DR CDD; cd06139; DNA_polA_I_Ecoli_like_exo; 1.
DR FunFam; 1.10.150.20:FF:000034; DNA polymerase I; 1.
DR FunFam; 3.30.420.10:FF:000051; DNA polymerase I; 1.
DR Gene3D; 3.30.70.370; -; 1.
DR Gene3D; 1.10.150.20; 5' to 3' exonuclease, C-terminal subdomain; 1.
DR Gene3D; 3.30.420.10; Ribonuclease H-like superfamily/Ribonuclease H; 1.
DR InterPro; IPR002562; 3'-5'_exonuclease_dom.
DR InterPro; IPR001098; DNA-dir_DNA_pol_A_palm_dom.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR002298; DNA_polymerase_A.
DR InterPro; IPR012337; RNaseH-like_sf.
DR InterPro; IPR036397; RNaseH_sf.
DR PANTHER; PTHR10133; DNA POLYMERASE I; 1.
DR PANTHER; PTHR10133:SF27; DNA POLYMERASE NU; 1.
DR Pfam; PF00476; DNA_pol_A; 2.
DR Pfam; PF01612; DNA_pol_A_exo1; 1.
DR PRINTS; PR00868; DNAPOLI.
DR SMART; SM00482; POLAc; 1.
DR SUPFAM; SSF56672; DNA/RNA polymerases; 1.
DR SUPFAM; SSF53098; Ribonuclease H-like; 1.
PE 2: Evidence at transcript level;
KW DNA damage {ECO:0000256|ARBA:ARBA00022763};
KW DNA repair {ECO:0000256|ARBA:ARBA00023204};
KW DNA replication {ECO:0000256|ARBA:ARBA00022705};
KW DNA-binding {ECO:0000256|ARBA:ARBA00023125};
KW DNA-directed DNA polymerase {ECO:0000256|ARBA:ARBA00022932};
KW Exonuclease {ECO:0000256|ARBA:ARBA00022839};
KW Hydrolase {ECO:0000256|ARBA:ARBA00022801};
KW Nuclease {ECO:0000256|ARBA:ARBA00022722};
KW Nucleotidyltransferase {ECO:0000256|ARBA:ARBA00022695};
KW Transferase {ECO:0000256|ARBA:ARBA00022679};
KW Transit peptide {ECO:0000256|ARBA:ARBA00022946}.
FT DOMAIN 882..1112
FT /note="DNA-directed DNA polymerase family A palm"
FT /evidence="ECO:0000259|SMART:SM00482"
FT REGION 210..232
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 1152 AA; 128640 MW; 2BD8424AB405F2A8 CRC64;
Query Match 99.9%; Score 5983; Length 1152;
Best Local Similarity 99.9%;
Matches 1151; Conservative 1; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MAFLGFSVQSSPFKPTSYLWFSPHSFSSSRSFWASSGKALHRREDCKTQSVENASSSLAV 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MAFLGFSVQSSPFKPTSYLWFSPHSFSSSRSFWASSGKALHRREDCKTQSVENASSSLAV 60
Qy 61 LGDSIKQISSHERKLFSSGLQHKIEEDSTYGWIAETNALKASKAKSSYNSYKKISAANCN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LGDSIKQISSHERKLFSSGLQHKIEEDSTYGWIAETNALKASKAKSSYNSYKKISAANCN 120
Qy 121 VSASTNRRVKDEFFDVPTEVNTRMMRERITSSYSATTCISGGNLSSKSKPPYNPAGGEKK 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VSASTNRRVKDEFFDVPTEVNTRMMRERITSSYSATTCISGGNLSSKSKPPYNPAGGEKK 180
Qy 181 VVGNWREYENHLPQVSVGLTHSRVNGARSVNKVDGSNVSHYKPLSKGSHLNGQLSSKIME 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VVGNWREYENHLPQVSVGLTHSRVNGARSVNKVDGSNVSHYKPLSKGSHLNGQLSSKIME 240
Qy 241 PKLEKVNKLREGHASDQLRHSVNGTETKVVTVKAKGVIQERAMNKMEKNVIQAVTADVMN 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PKLEKVNKLREGHASDQLRHSVNGTETKVVTVKAKGVIQERAMNKMEKNVIQAVTADVMN 300
Qy 301 GAEANAKGVILERATNKMEKNAIESMATDVVNGTKTRIVNDEGTGVSQVSLRERLGAMYD 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 GAEANAKGVILERATNKMEKNAIESMATDVVNGTKTRIVNDEGTGVSQVSLRERLGAMYD 360
Qy 361 KVHIVDNLSAAKEVVRKLTSQYRHLVHACDTEVAKIDVKQQTPVDHGEIICFSIYSGPEA 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 KVHIVDNLSAAKEVVRKLTSQYRHLVHACDTEVAKIDVKQQTPVDHGEIICFSIYSGPEA 420
Qy 421 DFGDGKSCIWVDVLDGDGKNLLVEFAPFFQDPSIRKVWHNYSFDNHVIENYGFKVSGFHA 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 DFGDGKSCIWVDVLDGDGKNLLVEFAPFFQDPSIRKVWHNYSFDNHVIENYGFKVSGFHA 480
Qy 481 DTMHMARLWDSSRRTSGGYSLEALTGDSTVMRDARPVHAERLFHGEGLFGKISMKTIFGR 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 DTMHMARLWDSSRRTSGGYSLEALTGDSTVMRDARPVHAERLFHGEGLFGKISMKTIFGR 540
Qy 541 KKLKKDGTEGKVTVIPSVEELQKTERELWICYSALDSISTLMLYESLKNKLAKRIWTFDG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 KKLKKDGTEGKVTVIPSVEELQKTERELWICYSALDSISTLMLYESLKNKLAKRIWTFDG 600
Qy 601 VRKGSMYEFYEKYWRPFGELLVQMETEGVLVDRAYLAEIEKVAKAEQQVAANRFRNWAAK 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 VRKGSMYEFYEKYWRPFGELLVQMETEGVLVDRAYLAEIEKVAKAEQQVAANRFRNWAAK 660
Qy 661 YCHDAKYMNVGSDTQLRQLFFGGIQNRKNSDESLPYEKEFKVPNIDKVTEEGKKAPTKFR 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 YCHDAKYMNVGSDTQLRQLFFGGIQNRKNSDESLPYEKEFKVPNIDKVTEEGKKAPTKFR 720
Qy 721 KIRLHRICDLIDTEMYTASGWPSVSGDALKALSGKVSADFDILDEADDNAEEDPETSIDE 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 KIRLHRICDLIDTEMYTASGWPSVSGDALKALSGKVSADFDILDEADDNAEEDPETSIDE 780
Qy 781 ALATNNEVPSQEPEVSIYGSAYNAFGGGQKGIEACHAIA ALCEMCSIGSLISNFILPLQG 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 ALATNNEVPSQEPEVSIYGSAYNAFGGGQKGIEACHAIA ALCEMCSIGSLISNFILPLQG 840
Qy 841 QDVSGENGRIHCSLNINTETGRLSARRPNLQNQPALEKDRYKIRQAFVAAQGNSLIVADY 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 QDVSGENGRIHCSLNINTETGRLSARRPNLQNQPALEKDRYKIRQAFVAAQGNSLIVADY 900
Qy 901 GQLELRILAHLANCKSMLDAFKAGGDFHSRTAMNMYTHIREAVENGQVLLEWHPQPGEEK 960
||||||||||||||||||||||||||||||||||||||||||||||:|||||||||||||
Db 901 GQLELRILAHLANCKSMLDAFKAGGDFHSRTAMNMYTHIREAVENGRVLLEWHPQPGEEK 960
Qy 961 PPVPLLKDAFGSERRKAKMLNFSIAYGKTTIGLARDWKVSVKEAKETVDRWYRDRKEVSD 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 PPVPLLKDAFGSERRKAKMLNFSIAYGKTTIGLARDWKVSVKEAKETVDRWYRDRKEVSD 1020
Qy 1021 WQEQRKFEAREFRRVHTLLGRARWFPSVKNATGSVKGHIERAAINTPVQGSAADVAMCAM 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 WQEQRKFEAREFRRVHTLLGRARWFPSVKNATGSVKGHIERAAINTPVQGSAADVAMCAM 1080
Qy 1081 LEISKNARLEELGWKLLLQVHDEVILEGPEESENEAMAIVVDCMSKPFGGKNILRVDLSV 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 LEISKNARLEELGWKLLLQVHDEVILEGPEESENEAMAIVVDCMSKPFGGKNILRVDLSV 1140
Qy 1141 DSKCAKNWYSAK 1152
||||||||||||
Db 1141 DSKCAKNWYSAK 1152
Prosecution Insights