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
Claims 1-3, 7, 8-11, 13, 18, 24-26, 34, 36, 40, 41, 43, 47, and 48 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-3, 7-11, 24-26, 34, 36, 47, and 48; and species, CB5 sequence SEQ ID NO:47 (1A), SEQ ID NO:50 (2A, 2A1), positions 64-104 of SEQ ID NO:1 having at most one or no histidine (3A), heterologous polynucleotide sequence SEQ ID NO:11 (4A), heterologous CB5 gene sequence SEQ ID NO:54 (5A), and CDS enzyme gene sequence SEQ ID NO:223 (6B, 6B1), in the reply filed on 12/12/2025 is acknowledged.
Claims 4 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/12/2025.
While performing a search of the elected species, SEQ ID NO:50, examiner also searched SEQ ID NO: 1-3, 58-63, 65 and 318, therefore, claims 3 and 9-10 are also examined and the restriction between these species is withdrawn.
Claims 1-3, 7-11, 13, 18, 24-26, 34, 36, 47, and 48 are examined.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 7-11, 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.
Claim 1 recites a host cell comprising a heterologous polynucleotide encoding cytochrome b5 (CB5), wherein the CB5 comprises the amino acid sequence of a, b, c, or d, which are protein fragments of 6-10 amino acids in length. However, the entire sequence of CB5 is not recited in the instant claims therefore, it is unclear what the amino acid sequence of CB5 is. It is unclear where the amino acids of a-d are located within the CB5 protein sequence. One of ordinary skill in the art would not know what amino acid sequence of the claimed CB5 is.
Claims 2, 3, 7-11, 24-26, 34, 36, 47, and 48 depend from claim 1 and are also rejected.
Similarly, claims 2, 3, and 18 recite the host cell of claim 1 wherein CB5 comprises the amino acid sequence of a-c, a-d, and a-d, respectively. However, the entire sequence of CB5 is not recited in the instant claims, therefore, it is unclear what the amino acid sequence of CB5 is. It is unclear where the amino acids of a-c, a-d, and a-d are located within the wild type CB5 protein sequence. One of ordinary skill in the art would not know what amino acid sequence of the claimed CB5 is.
Claim 7 recites the host cell of claim 1 wherein the CB5 comprises at most one histidine in one or more of the following regions a-c, which recite regions corresponding to positions of SEQ ID NO:1. It is unclear if the claim means that the CB5 amino acid sequence is SEQ ID NO:1.
Claim 8 recites the host cell of claim 7 wherein the CB5 comprises no histidine residues in regions a-c, which recite regions corresponding to positions of SEQ ID NO:1. It is unclear if the claim means that the CB5 amino acid sequence is that of SEQ ID NO:1.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 47 and 48 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 47 does not further limit claim 1, as claim 1 inherently requires a host cell comprising mogrol because claim 1 recites a host cell for producing mogrol; and claim 47 recites wherein the host cell comprises mogrol.
Claim 48 recites that the host cell of claim 1 comprises a curcurbitadienol synthase (CDS) enzyme; and claim 1 recites a host cell comprising a heterologous polynucleotide encoding a cytochrome b5 (CB5). Claim 48 does not include all limitations of claim 1, as the claim can be interpreted to require that the host cell of claim 1 comprises another enzyme, curcurbitadienol synthase enzyme. Applicant may amend claim 48 to recite: The host cell of claim 1, further comprising a cucurbitadienol synthase (CDS) enzyme.
Applicant may cancel the claims, amend the claims to place the claims in proper dependent form, rewrite the claims in independent form, or present a sufficient showing that the dependent claims comply with the statutory requirements.
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 1-3, 7-11, 13, 18, 24-26, 34, 36, 47, and 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 claims contain 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 applications subject to pre-AIA 35 U.S.C. 112, the inventors, at the time the application was filed, had possession of the claimed invention.
Claims 1-3, 7-11, 24-26, 34, 36, 47, and 48 are drawn to a host cell comprising a heterologous polynucleotide encoding a cytochrome b5 (CB5), wherein the CB5 comprises various polypeptide fragments. Claim 9 recites that the CB5 comprises a sequence that is at least 90% identical to any one of SEQ ID NOs:1-3, and 318. Claim 10 recites that the CB5 comprises the sequence of any one of SEQ ID NOs:1-3 and 319. Claim 11 recites that the heterologous polynucleotide comprises a sequence that is at least 90% identical to any one of SEQ ID NOs:11-14, 22-24, 316-317, and 330-331. Because claim 10 recites “the CB5 comprises”, the claim encompasses CB5 protein sequences that comprise other amino acids in addition to SEQ ID NOs:1-3 and 318. Claim 13 is drawn to a host cell for producing mogrol comprising a heterologous polypeptide encoding a CB5 protein, wherein the CB5 protein comprises a sequence that is at least 90% identical to SEQ ID NOs:1-10 and 318 and/or the heterologous polypeptide comprises a sequence that is at least 90% identical to any one of SEQ ID NOs: 11-24, 316-317, and 330-331. Claim 18 is drawn to a host cell comprising a CB5 protein comprising the amino acid sequence of SEQ ID NO:54, 55, 56, or 57.
Claim 25 further requires that the host cell comprises one or more heterologous polynucleotides encoding one or more of: a UDP-glycosyltransferase (UGT) enzyme, a cucurbitadienol synthase (CDS) enzyme, a C11 hydroxylase, a cytochrome P450 reductase, an epoxide hydrolase (EPH), a lanosterol synthase, and a squalene epoxidase (SQE). Claim 26, which depends from claim 25, recites that the UGT enzyme comprises a sequence that is at least 90% identical to SEQ ID NO:121, the CDS enzyme comprises a sequence that is at least 90% identical to any one of SEQ ID NOs:226, 235, and 232, the C11 hydroxylase comprises a sequence that is at least 90% identical to any one of SEQ ID NOs:280-281, 305, 315, and 324, the cytochrome P450 reductase comprises a sequence that is at least 90% identical to any one of SEQ ID NOs:282-283 and 306-307, the EPH comprises a sequence that is at least 90% identical to any one of SEQ ID NOs:284-292 and 309-310, the lanosterol synthase comprises a sequence that is at least 90% identical to SEQ ID NO:329 or 336, and/or the SQE comprises a sequence that is at least 90% identical to any one of SEQ ID NOs:293-295, 312, or 328.
MPEP 2163.05 II states “the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species. A ‘representative number of species’ means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that ‘only describe[d] one type of structurally similar antibodies’ that ‘are not representative of the full variety or scope of the genus.’). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us].’”
The instant specification reduces to practice 5 CB5 proteins (SEQ ID NOs:1-4 and 318) that increase mogrol production in their parental strain (p. 59, Table 3; p. 60, Table 4). The specification does not disclose the entire genus of claimed CB5 variants comprising the polypeptide fragments of claims 1-3. The specification dose not disclose amino acids sequences with up to 10% divergence from SEQ ID NO:1-3 or 318, or disclose polynucleotides with up to 10% divergence from SEQ ID NOs:11-24, 316-317, and 330-331. The specification does not disclose all variants with up to 10% divergence from the claimed amino acid sequences of UDP-glycosyltransferase (UGT), cucurbitadienol synthase (CDS), C11 hydroxylase, cytochrome P450 reductase, epoxide hydrolase (EPH), lanosterol synthase, or squalene epoxidase (SQE). The instant specification does not disclose what structural properties the claimed CB5 protein requires for the cell to produce mogrol, or disclose which regions of the recited sequences are the active site residue(s) for conserving claimed activity. Therefore, the disclosed species are not representative of the entire genus of claimed variants.
There are no prior art references that teach sequences with 90% sequence identity to instant SEQ ID NO:1-10 or 318, or SEQ ID NOs:11-24, 316-317, or 330-331. There are no prior art references that teach that cytochrome B5 variants increase mogrol production in their host cells.
In summary, neither the instant specification, nor the prior art, discloses a structure-function relationship between conserved amino acid residues in the claimed CB5 structure and its ability to increase mogrol production in its host. One of ordinary skill in the art cannot reasonably predict which residues of CB5 may be modified to generate increased mogrol. One of ordinary skill in the art cannot reasonably predict which residues of the amino acid sequences of UDP-glycosyltransferase (UGT), cucurbitadienol synthase (CDS), C11 hydroxylase, cytochrome P450 reductase, epoxide hydrolase (EPH), lanosterol synthase, or squalene epoxidase (SQE) as recited in instant claim 26 may be modified to generate functional enzymes. Based on the instant disclosure, those skilled in the art would not conclude that the applicant was in possession of host cells comprising all claimed CB5 variants and all claimed UDP-glycosyltransferase (UGT), cucurbitadienol synthase (CDS), C11 hydroxylase, cytochrome P450 reductase, epoxide hydrolase (EPH), lanosterol synthase, or squalene epoxidase (SQE) variants.
Examiner Comment
The Examiner is not aware of any prior art references that teach host cells for increasing mogrol production comprising a CB5 protein comprising any one of SEQ ID NOs:47-65, as recited in instant claims 1, 2, 3, and 18. There are no prior art references that teach a host cell comprising CB5, wherein the amino acid sequence of the CB5 is 100% identical to instant SEQ ID NOs:1-10, or 318. There are no prior art references that teach a CB5 polynucleotide with 100% sequence identity to instant SEQ ID NOs:11-24, 316-317, or 330-331. There are no prior art references that teach a relationship between cytochrome B5 comprising the full length sequences of the claimed SEQ ID NO:’s and mogrol production.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHEL EMILY MARTIN whose telephone number is (703)756-1416. The examiner can normally be reached M-Th 8:30-16:00, F 8:30-10:00 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Louise Humphrey can be reached at (571) 272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/RACHEL EMILY MARTIN/Examiner, Art Unit 1657
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