DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 7 and 10-24 are pending in the application.
Applicant’s amendment to the claims, filed January 29, 2026, is acknowledged. This listing of the claims replaces all prior versions and listings of the claims. Regarding claims 12 and 13, applicant is reminded that double brackets can be used to show deletion of five or fewer consecutive characters and regarding claim 12, part (b), double brackets are used to show deletion of characters. See MPEP 714.II.C.(B).
Applicant’s amendment to the specification, filed January 29, 2026, is acknowledged.
Applicant’s remarks filed January 29, 2026 in response to the non-final rejection filed October 29, 2026 are acknowledged and have been fully considered.
Rejections previously applied to claims 1-6, 8, and 9 are withdrawn in view of applicant’s amendment to cancel these claims.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Restriction/Election
In response to a requirement for restriction/election, applicant elected without traverse the invention of Group I, corresponding to pending claims 7, 10-15, and 19-24, species (A-1), and species (D) in the reply filed September 24, 2025.
Claims 16-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 7, 10-15, and 19-24 are being examined on the merits with claims 7, 12, 13, 20, and 22-24 being examined only to the extent they read on the elected subject matter. In the interest of clarity, it is noted that rejections set forth below may be directed to a non-elected species, which has yet to be searched and examined on the merits because the cited prior art was identified during a search and examination of the elected species as set forth above.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on December 19, 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS has been considered by the examiner.
Specification/Informalities
The objection to the specification is withdrawn in view of applicant’s amendment to the specification to remove hyperlinks.
Claim Objections
The objections to claims 12 and 13 for reciting abbreviations and the grammatically incorrect phrase “one of the followings” are withdrawn in view of applicant’s amendment to recite the full phrases for which the abbreviations are used in claims 12 and 13 and to recite “one of the following” in claim 13.
Claim 7 is objected to in the recitation of “CPTL6” and “CPTL7” as abbreviations for “cis-prenyltransferase 6” and “cis-prenyltransferase 7” because the abbreviations for “cis-prenyltransferase 6” and “cis-prenyltransferase 7” are “CPT6” and “CPT7,” respectively.
Claim 10 is objected to in the recitation of “lipid structure” and in the interest improving claim form and consistency with claim 7, it is suggested that the noted phrase be amended to recite “lipid membrane structure.”
Claims 12, 13, 20, 22, and 23 are objected to in the recitation of “or more identity” (e.g., line 5 of claim 12) and in the interest improving claim form and consistency with claim 7, it is suggested that the noted phrase be amended to recite “or more sequence identity.” Addressing claims 12 and 13, applicant states the issue noted in the objection has been addressed, however, claims 12 and 13 still recite the phrase “or more identity.”
Claim 15 is objected to in the recitation of “comprising a lipid membrane structure, which is a proteoliposome comprising the protein composition and a phospholipid” and in the interest improving claim form, it is suggested that the noted phrase be amended to recite “further comprising a phospholipid.”
Claim 19 is objected to in the recitation of “comprises a phospholipid” and in the interest improving claim form, it is suggested that the noted phrase be amended to recite “further comprises a phospholipid.”
Claim 23 is objected to in the recitation of “the protein (D) encoded by” and in the interest improving claim form and grammar, it is suggested that the noted phrase be amended to recite “the protein (D) is encoded by.”
Claim Rejections - 35 USC § 112(b)
The rejection of claims 12 and 13 under 35 U.S.C. 112(b) as being indefinite in the recitation of “exhibits the same activity” or “exhibiting the same activity” as CPT6, CPTL, or CPT2 is withdrawn in view of applicant’s amendments to claims 12 and 13 to recite “a protein exhibiting 50% or more of the same isoprene polymerization activity…”;
the rejection of claims 10-15 for reciting “cell expressing a protein constituting the protein composition of claim 1” is withdrawn in view of the applicant’s amendment to claim 10 to delete the phrase “expressing a protein constituting the protein composition of claim 1”;
the rejection of claims 12 and 13 as lacking antecedent basis for "the polynucleotide” is withdrawn in view of applicant’s amendment to claims 12 and 13 to depend from claim 11; and
the rejection of claim 14 as lacking antecedent basis for "the expression unit” is withdrawn in view of applicant’s amendment to claims 12 and 13 to depend from claim 11.
Claim 13 is newly rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention. This rejection is necessitated by applicant’s amendment to claim 10 to delete the phrase “a protein constituting the protein composition.”
Claim 13 recites the limitation “the protein constituting the protein composition” in line 2. There is insufficient antecedent basis for this limitation in the claim. Applicant may consider amending the phrase “wherein the polynucleotide is the polynucleotide encoding the protein constituting the protein composition, and further comprises at least one of the following:” in lines 1-3 of claim 13 to recite “wherein the cell further comprises at least one of the following:”.
Claim Rejections - 35 USC § 102/103
Claims 7, 10, 11, 13-15, and 19-24 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Yamaguchi et al. (US 2018/0171364 A1; cited on the IDS filed on October 19, 2022; hereafter “Yamaguchi”).
As amended, claims 7 and 19-24 are drawn to (in relevant part) a lipid membrane structure comprising a protein composition, wherein:
the protein composition comprising protein (B) and protein (A-1):
(A-1) is one or more protein selected from proteins comprising an amino acid sequence of SEQ ID NO: 6 and proteins comprising an amino acid sequence having 90% or more sequence identity with the amino acid sequence of SEQ ID NO: 6 and exhibiting 50% or more of the same isoprene polymerization activity as cis-prenyltransferase 6 (CPTL6); and
(B) is one or more protein selected from proteins comprising an amino acid sequence of SEQ ID NO: 10 and proteins comprising an amino acid sequence having 90% or more sequence identity with the amino acid sequence of SEQ ID NO: 10 and exhibiting 50% or more of the same isoprene polymerization activity as cis-prenyltransferase-like (CPTL);
wherein the structure is a proteoliposome.
As amended, claims 10, 11, and 13-15 are drawn to a cell comprising the lipid structure of claim 7.
Regarding claims 7, 10, and 11, Yamaguchi teaches a “Second Invention” that relates to a vector comprising a gene coding for a Nogo-B receptor (NgBR) family protein and a gene coding for a cis-prenyltransferase (CPT) family protein (paragraph [0302]).
Yamaguchi teaches the CPT family protein is particularly preferably derived from Hevea brasiliensis (paragraph [0072]). Yamaguchi teaches the CPT family protein CPT4 from Hevea brasiliensis comprising the amino acid sequence of SEQ ID NO: 37 (paragraphs [0060] and [0738] and Figure 5). SEQ ID NO: 37 of Yamaguchi has greater than 99% sequence identity to instant SEQ ID NO: 6 (see Appendix A of the Office action filed October 29, 2025). Yamaguchi does not explicitly teach CPT4 of SEQ ID NO: 37 exhibits 50% or more of the same isoprene polymerization activity as CPT6. However, since the amino acid sequence of CPT4 of Yamaguchi (i.e., SEQ ID NO: 37 of Yamaguchi) is substantially identical to instant SEQ ID NO: 6, it is presumed that CPT4 of Yamaguchi exhibits 50% or more of the same isoprene polymerization activity as instant CPT6. See MPEP 2112.01.I.
Yamaguchi teaches the NgBR family protein is particularly preferably derived from Hevea brasiliensis (paragraph [0072]). Yamaguchi teaches the NgBR family protein from Hevea brasiliensis (HRTBP) comprising the amino acid sequence of SEQ ID NO: 4 (paragraphs [0187] and [0733]). SEQ ID NO: 4 of Yamaguchi has 100% sequence identity to instant SEQ ID NO: 10 (see Appendix B of the Office action filed October 29, 2025). Yamaguchi does not explicitly teach HRTBP of SEQ ID NO: 4 exhibits 50% or more of the same isoprene polymerization activity as CPTL. However, since the amino acid sequence of HRTBP of Yamaguchi (i.e., SEQ ID NO: 4 of Yamaguchi) is substantially identical to instant SEQ ID NO: 10, it is presumed that HRTBP of Yamaguchi exhibits 50% or more of the same isoprene polymerization activity as instant CPTL. See MPEP 2112.01.I.
Yamaguchi teaches introducing the vector of the “second invention” into plant cells or a yeast for production of polyisoprenoid (paragraphs [0339] and [0340]). Yamaguchi teaches that in yeasts and non-rubber-producing plants, the products synthesized by the CPT family proteins transfer from the hydrophobic cleft structures of the CPT family proteins into the lipid bilayers of cells and accumulate in the lipid bilayers (paragraphs [0182] and [0183]). Yamaguchi teaches NgBR family proteins bind to a membrane via one or more transmembrane domains and interact with the CPT family protein (paragraph [0186]).
The instant specification defines “proteoliposome” as referring to an artificial vesicle in which a protein is encapsulated or bound to a portion of the lipid bilayer of liposome (p. 20, paragraph [0026]) and further discloses “[t]he cell containing proteoliposome can be produced by interacting the proteoliposome with the cell membrane. Examples of the methods for the interaction include adsorption or binding of the liposome to the cell surface, uptake of the liposome into the cell (endocytosis or phagocytosis), and fusion of the lipid bilayer membrane of the liposome with the cell membrane” (pp. 23-24, paragraph [0039]). Given a broadest reasonable interpretation in light of the specification’s description of “proteoliposome,” claim 7 encompasses a cell comprising the proteoliposome lipid bilayer integrated within a native lipid bilayer of the cell that is indistinguishable from a lipid bilayer comprising a CPT family protein interacting with a NgBR family protein of Yamaguchi’s yeast cell or non-rubber-producing plant cell comprising the vector of the “second invention.” Since the Office does not have the facilities for examining and comparing applicants’ claimed lipid membrane structure and cell with the lipid membrane structure and cell of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the lipid membrane structure and cell of the prior art does not possess the same material structural and functional characteristics of the claimed lipid membrane structure and cell). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
Regarding claims 13, 21, and 22, Yamaguchi teaches the CPT family protein and NgBR family protein bind to rubber particles and produce a polyisoprenoid (paragraph [0050]). Yamaguchi teaches that binding the CPT family protein and NgBR family protein to rubber particles is expected to stabilize and increase the activity of the CPT family protein (paragraph [0050]). Yamaguchi teaches that in the binding step, other proteins may further be bound to the rubber particles (paragraph [0229]), which are preferably proteins that inherently exist on rubber particles in rubber-producing plants (paragraph [0231]), which are exemplified by rubber elongation factor (REF) and small rubber particle protein (SRPP) (paragraph [0232]). Yamaguchi teaches REF is encoded by the nucleotide sequence of SEQ ID NO:27 (paragraph [0440]). SEQ ID NO: 27 of Yamaguchi has 100% sequence identity to instant SEQ ID NO: 13 (see Appendix D of the Office action filed October 29, 2025). Yamaguchi does not explicitly teach REF of SEQ ID NO: 27 exhibits 50% or more of the same isoprene polymerization activity as REF2. However, since the amino acid sequence of REF of Yamaguchi (i.e., SEQ ID NO: 27 of Yamaguchi) is substantially identical to instant SEQ ID NO: 13, it is presumed that REF of Yamaguchi exhibits 50% or more of the same isoprene polymerization activity as instant REF2. See MPEP 2112.01.I.
Regarding claim 14, Yamaguchi teaches the CPT family protein CPT4 from Hevea brasiliensis (paragraphs [0060] and [0738] and Figure 5) and the NgBR family protein from Hevea brasiliensis (HRTBP) (paragraphs [0187] and [0733]), which are heterologous to a yeast and non-rubber-producing plant cells and thus, the vector of Yamaguchi’s “second invention” is considered to be a “heterologous” expression unit.
Regarding claims 15 and 19, Yamaguchi acknowledges that lipid bilayer membranes are formed of phospholipids (paragraph [0236]).
Regarding claim 20, given that there are only three amino acid differences between SEQ ID NO: 37 of Yamaguchi and instant SEQ ID NO: 6 (see Appendix A of the Office action filed October 29, 2025) and given the degeneracy of the genetic code, SEQ ID NO: 37 of Yamaguchi is necessarily encoded by a polynucleotide comprising a nucleic acid sequence having 90% or more sequence identity with the nucleic acid sequence of SEQ ID NO: 5.
Regarding claim 23, given that SEQ ID NO: 28 of Yamaguchi is identical to instant SEQ ID NO: 14 (see Appendix C of the Office action filed October 29, 2025), and given the degeneracy of the genetic code, SEQ ID NO: 28 of Yamaguchi is necessarily encoded by a polynucleotide comprising a nucleic acid sequence having 90% or more sequence identity with the nucleic acid sequence of SEQ ID NO: 13.
Regarding claim 24, Yamaguchi teaches Hevea brasiliensis is para rubber tree (paragraph [0002]) and teaches the REF of SEQ ID NO: 28, which is from Hevea brasiliensis (paragraph [0736]).
Therefore, Yamaguchi anticipates claims 7, 10, 11, 13-15, and 19-24 as written.
Alternatively, in view of the cited teachings of Yamaguchi, the lipid membrane structure and cell of claims 7, 10, 11, 13-15, 19, and 21-24 would have been obvious to one of ordinary skill in the art before the effective filing date. One would have been motivated and expected success to make the lipid membrane structure and cell of claims 7, 10, 11, 13-15, and 19-24 because of the explicit teachings of Yamaguchi as set forth above.
Therefore, claims 7, 10, 11, 13-15, and 19-24 are anticipated by or, in the alternative, are obvious in view of Yamaguchi.
Claim Rejections - 35 USC § 103
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Yamaguchi as evidenced by GenBank Database Accession Number LC613086 (April 2023, 1 page; cited on the attached Form PTO-892; hereafter “GenBank”).
Claim 12 is drawn to (in relevant part) the cell according to claim 10, wherein the polynucleotide comprises (b) and (a-1):
(a-1) is one or more polynucleotide selected from a polynucleotide(s) comprising a nucleic acid sequence of SEQ ID NO: 5 and a polynucleotide that comprises a nucleic acid sequence having 90% or more identity with the nucleic acid sequence of SEQ ID NO: 5 and encodes a protein exhibiting 50% or more of the same isoprene polymerization activity as cis-prenyltransferase (CPT6); and
(b) one or more polynucleotide(s) selected from a polynucleotide(s) comprising a nucleic acid sequence of SEQ ID NO: 9 and a polynucleotide(s) that comprises a nucleic acid sequence having 90% or more identity with the nucleic acid sequence of SEQ ID NO: 9 and encodes a protein exhibiting 50% or more of the same isoprene polymerization activity as cis-prenyltransferase-like (CPTL).
The relevant teachings of Yamaguchi as applied to claims 7, 10, 11, 13-15, and 19-24 are set forth above.
Regarding polynucleotide (a-1) of claim 12, Yamaguchi teaches the CPT family protein CPT4 from Hevea brasiliensis comprising the amino acid sequence of SEQ ID NO: 37 (paragraphs [0060] and [0738] and Figure 5), which has greater than 99% sequence identity to instant SEQ ID NO: 6 (see Appendix A sequence alignment).
Regarding polynucleotide (b) of claim 12, Yamaguchi further teaches the nucleotide sequence of the cDNA for HRTBP is SEQ ID NO: 3 (Example 1 at paragraph [0366]). SEQ ID NO: 3 of Yamaguchi has greater than 99% sequence identity to instant SEQ ID NO: 9 (see Appendix D of the Office action filed October 29, 2025).
Yamaguchi further teaches conventional techniques for obtaining a cDNA and identifying the nucleotide sequence encoding the protein (paragraph [0226]).
The difference between Yamaguchi and claim 12 is that Yamaguchi does not explicitly teach obtaining a cDNA and identifying the nucleotide sequence for CPT4 from Hevea brasiliensis.
In view of the teachings of Yamaguchi, it would have been obvious to one of ordinary skill in the art to obtain a cDNA and identify the nucleotide sequence encoding the CPT4 from Hevea brasiliensis. One would have been motivated and would have expected success because Yamaguchi taught CPT4 from Hevea brasiliensis and taught using conventional techniques for obtaining a cDNA and identifying the nucleotide sequence encoding the protein. Although Yamaguchi does not teach or suggest the cDNA sequence of CPT4 from Hevea brasiliensis has greater than 90% sequence identity to instant SEQ ID NO: 5, according to MPEP 2112, “The express, implicit, and inherent disclosures of a prior art reference may be relied upon in the rejection of claims under 35 U.S.C. 102 or 103” and evidentiary reference GenBank is cited to show that the cDNA sequence of CPT4 from Hevea brasiliensis has greater than 90% sequence identity to instant SEQ ID NO: 5 (see Appendix E of the Office action filed October 29, 2025).
Therefore, the cell of claim 12 would have been obvious to one of ordinary skill in the art before the effective filing date.
RESPONSE TO REMARKS: In response to the prior art rejections, applicant argues the rejections are obviated by amendment to claim 7, particularly the amendment to recite “proteoliposome.” Applicant argues that in contrast to the claimed invention, Yamaguchi is directed to natural rubber biosynthesis. Applicant argues the claimed invention would have been unpredictable from Yamaguchi because while the claimed invention exhibits good isoprene polymerization activity, Yamaguchi’s reference examples 7 and 8 only confirmed production of an isoprene polymer having a short chain.
Applicant’s arguments are not found persuasive. For the reasons stated above, claims 7, 10-15, and 19-24 are anticipated by or are obvious in view of the cited prior art. While applicant takes the position that the claimed lipid membrane structure and cell are distinguished over the cited prior art by the length of the isoprene polymerization product, there is no requirement that the claimed lipid membrane structure and cell produce an isoprene polymerization product. Moreover, applicant compares an isoprene polymerization product of Yamaguchi’s Examples 7 and 8 with an isoprene polymerization product produced by a cell-free proteoliposome of the Examples of the specification (e.g., specification at p. 28, line 31 to p. 30, line 25), however, the claims do not require a cell-free proteoliposome as disclosed in the instant specification. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See MPEP 2145.VI.
For these reasons, it is the examiner’s position that claims 7, 10-15, and 19-24 are anticipated by or are obvious in view of the cited prior art.
Claim Rejections - 35 USC § 101
The rejection of claims 7 and 10-13 under 35 U.S.C. 101 is withdrawn in view of applicant’s amendment to claim 7 to recite “wherein the structure is a proteoliposome” and applicant’s amendments to claims 10-13 to depend directly or indirectly from claim 7.
Conclusion
Status of the claims:
Claims 7 and 10-24 are pending in the application.
Claims 16-18 are withdrawn from consideration.
Claims 7, 10-15, and 19-24 are rejected.
No claim is in condition for allowance.
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 DAVID J STEADMAN whose telephone number is (571)272-0942. The examiner can normally be reached Monday to Friday, 7:30 AM to 4:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MANJUNATH N. RAO can be reached at 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/David Steadman/Primary Examiner, Art Unit 1656