DETAILED CORRESPONDENCE
Status of the Application
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on June 5, 2026 has been entered.
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 June 5, 2026, is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Applicant’s remarks filed June 5, 2026 in response to the final rejection filed March 5, 2026 are acknowledged and have been fully considered.
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 filed July 28, 2025, 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Claims 16-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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.
Claim Objections
The objection to claim 7 for the recitation of “CPTL6” and “CPTL7” is withdrawn in view of applicant’s amendment to claim 7 to recite “CPT6” and “CPT7,” respectively,
the objection to claim 10 for the recitation of “lipid structure” is withdrawn in view of applicant’s amendment to claim 10 to recite “lipid membrane structure,”
the objection to claims 12, 13, 20, 22, and 23 for reciting “or more identity” is withdrawn in view of applicant’s amendments to claims 12, 13, 20, 22, and 23 to recite “or more sequence identity,”
the objection to claim 15 for reciting “comprising a lipid membrane structure, which is a proteoliposome comprising the protein composition and a phospholipid” is withdrawn in view of applicant’s amendment to claim 15 to recite “further comprising a lipid membrane structure, which is a proteoliposome comprising the protein composition and a phospholipid,”
the objection to claim 19 for reciting “comprises a phospholipid” is withdrawn in view of applicant’s amendment to claim 19 to recite “further comprises a phospholipid,” and
the objection to claim 23 for reciting “the protein (D) encoded by” is withdrawn in view of applicant’s amendment to claim 23 to recite “the protein (D) is encoded by.”
Claim 15 is objected to for the recitation of “further comprising a lipid membrane structure, which is a cell-free proteoliposome comprising the protein composition and a phospholipid” and in the interest of improving claim form, it is suggested that the noted phrase be amended to recite “wherein the cell-free proteoliposome further comprises a phospholipid.”
Claim Rejections - 35 USC § 112(b)
The rejection of claim 13 under 35 U.S.C. 112(b) as lacking antecedent basis for the limitation “the protein constituting the protein composition” is withdrawn in view of applicant’s amendment to claim 13 to delete the phrase “is the polynucleotide encoding the protein constituting the protein composition.”
Claims 10-15 are 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 7 to recite “wherein the structure is a cell-free proteoliposome.”
As amended, claim 7 recites a “lipid membrane structure…wherein the structure is a cell-free proteoliposome.” Claims 10-15 are confusing as being drawn to a “cell” comprising the lipid membrane structure of claim 7 while the lipid membrane structure of claim 7 is a “cell-free proteoliposome.”
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.
Claims 10-15 are newly rejected under 35 U.S.C. 112(a) as failing to comply with the enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. This rejection is necessitated by applicant’s amendment to claim 7 to recite “wherein the structure is a cell-free proteoliposome.”
“The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue.” In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976). Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)) as follows: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01(a). The Factors most relevant to the instant rejection are addressed in detail below.
The nature of the invention: The instant specification discloses that according to prior art technology, it is necessary to collect rubber particles from plants, which makes the process of collecting rubber particles complicated, and it is difficult to stabilize the quality of rubber particles because they are extracted from plants, and some embodiments of the present disclosure provide a means for efficiently producing natural rubber and stably providing the same, and is aimed at stably providing a rubber resource (paragraphs [0006] and [0007]).
The breadth of the claims: As amended, claims 10-15 are drawn to (in relevant part) a cell for producing an isoprene polymerization product comprising a lipid membrane structure, wherein the lipid membrane structure comprises 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 cell-free proteoliposome.
Claims 10-15 require a cell comprising a cell-free proteoliposome.
The amount of direction provided by the inventor; The existence of working examples: The specification fails to disclose a working example of a cell comprising a “cell-free proteoliposome” as encompassed by claims 10-15.
The state of the prior art; The level of one of ordinary skill; and The level of predictability in the art: One of skill in the art would recognize that a cell cannot comprise a “cell-free proteoliposome.”
Applicants have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention. Without sufficient guidance, determination of having the desired biological characteristics is 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).
Claims 10-15 are newly rejected under 35 U.S.C. 112(a) 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 at the time the application was filed, had possession of the claimed invention. This rejection is necessitated by applicant’s amendment to claim 7 to recite “wherein the structure is a cell-free proteoliposome.”
MPEP 2163.II.A.2.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163 states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
MPEP § 2163 further states that “[s]atisfactory 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.’ Such correlations may be established ‘by the inventor as described in the specification,’ or they may be ‘known in the art at the time of the filing date.’"
The factors considered in the Written Description requirement are (1) level of skill and knowledge in the art, (2) partial structure, (3) physical and/or chemical properties, (4) functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the (5) method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient." MPEP § 2163.
As amended, claims 10-15 are drawn to (in relevant part) a cell for producing an isoprene polymerization product comprising a lipid membrane structure, wherein the lipid membrane structure comprises 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 cell-free proteoliposome.
Claims 10-15 require a cell comprising a cell-free proteoliposome.
The specification and prior art of record fail to disclose a representative species of a cell comprising a cell-free proteoliposome as encompassed by claims 10-15 and given the inconsistent recitation of a “cell” comprising a “cell-free proteoliposome,” one of skill in the art would reasonably conclude that the applicant was not in possession of the claimed invention.
Claim Rejections - 35 USC § 102/103
The rejection of claims 7, 10, 11, 13-15, and 19-24 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”) is withdrawn in view of applicant’s amendment to claim 7 to recite “wherein the structure is a cell-free proteoliposome.” Yamaguchi does not explicitly teach a cell-free proteoliposome.
Claim Rejections - 35 USC § 103
The rejection of claim 12 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”) is withdrawn in view of applicant’s amendment to claim 7 to recite “wherein the structure is a cell-free proteoliposome.” Yamaguchi does not explicitly teach a cell-free proteoliposome.
Claims 7 and 19-24 are newly rejected under 35 U.S.C. 103 as being unpatentable over Yamaguchi in view of ENDEXT® Technology ProteoLiposome Expression Kit Instruction Manual (CellFree Sciences Co., 2016, 25 pages; cited on the attached Form PTO-892; hereafter “Instruction Manual”).
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 cell-free proteoliposome.
Regarding instant claim 7, Yamaguchi teaches natural rubber is an example of a polyisoprenoid and is obtained by cultivating rubber-producing plants (paragraph [0002]), however, there is concern that natural rubber sources will dry up (paragraph [0003]). Yamaguchi teaches methods for producing a polyisoprenoid by enhancing the rubber synthesis activity of rubber particles or producing a polyisoprenoid by recombinant techniques (paragraphs [0020]-[0021]).
Yamaguchi teaches a “First Invention,” which is a method for producing a polyisoprenoid by binding a protein expressed by a gene coding for a cis-prenyltransferase (CPT) family protein and a protein expressed by a gene coding for a Nogo-B receptor (NgBR) family protein to rubber particles in vitro (paragraph [0062]).
Yamaguchi teaches the rubber particles are derived from the latex of a rubber-producing plant such as Hevea brasiliensis, Taraxacum kok-saghyz, Parthenium argentatum, Sonchus oleraceus, or Ficus elastica. (paragraph [0068]).
Yamaguchi teaches the binding step may be carried out by performing protein synthesis in the presence of both rubber particles and a cell-free protein synthesis solution containing an mRNA coding for the CPT family protein and an mRNA coding for the NgBR family protein to bind the CPT family protein and the NgBR family protein to the rubber particles (paragraph [0233]).
Yamaguchi teaches the cell-free protein synthesis solution preferably contains a germ extract, which is preferably derived from wheat (paragraphs [0037]-[0038]).
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 a “Second Invention,” which is a method for producing a polyisoprenoid using 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]; the NgBR family protein and CPT family protein are described by Yamaguchi as noted above).
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]).
Yamaguchi does not explicitly teach a cell-free proteoliposome.
While Yamaguchi’s “First Invention” involves the use of rubber particles derived from the latex of a rubber-producing plant (paragraphs [0062] and [0068]), one of ordinary skill in the art would have recognized a shortcoming of Yamaguchi’s “First Invention” is the requirement for rubber particles derived from the latex of a rubber-producing plant as Yamaguchi’s own disclosure acknowledges the concern that natural rubber sources will dry up (paragraph [0003]).
Also, while Yamaguchi’s “Second Invention” involves the use of a plant or yeast cell as an expression host to accumulate the NgBR family protein and the CPT family protein, which are membrane proteins, into the lipid bilayer (paragraphs [0182], [0183], [0185], and [0186]), one of ordinary skill in the art would have recognized a shortcoming of Yamaguchi’s “Second Invention” in view of Instruction Manual, which teaches that expression of eukaryotic membrane proteins presents challenges caused by complications to express those proteins in standard protein expression systems, where membrane proteins can be toxic to cell system used or form insoluble aggregates (p. 2, top).
Instruction Manual teaches these problems can be addressed by using the wheat germ cell-free protein expression system offered by CellFree Sciences. According to Instruction Manual, by adding liposomes to the translation reaction, membrane proteins are directly inserted into the lipid bilayer of the liposome to form proteoliposome complexes (p. 2, top). Instruction Manual teaches a kit that provides all necessary reagents to prepare proteoliposome complexes for proteins of interest and the proteoliposomes can be easily isolated by centrifugation (p. 2, top).
In view of the combined teachings of Yamaguchi and Instruction Manual, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify Yamaguchi to make a cell-free proteoliposome comprising the CPT family protein and the NgBR family protein. One would have been motivated to do this because one of ordinary skill in the art would have recognized shortcomings of Yamaguchi’s “First Invention” and “Second Invention,” while Instruction Manual teaches cell-free production of membrane proteins with liposomes to form a proteoliposome complex, which does not suffer from the shortcomings of using natural rubber particles and standard cell-based protein expression systems of Yamaguchi’s “First Invention” and “Second Invention.” One would have had a reasonable expectation of success because Instruction Manual taught a kit that provides all necessary reagents to prepare proteoliposome complexes for proteins of interest and taught the proteoliposomes can be easily isolated.
Regarding instant claim 19, Yamaguchi acknowledges that lipid bilayer membranes are formed of phospholipids (paragraph [0236]).
Regarding instant 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 instant claims 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 instant 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 instant 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, the invention of claims 7 and 19-24 would have been obvious to one of ordinary skill in the art before the effective filing date.
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.
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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/David Steadman/Primary Examiner, Art Unit 1656
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