DETAILED ACTION
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 .
Election/Restrictions and Claim Status
Applicants’ amendments and arguments filed 9/24/25 are acknowledged. Any objection or rejection from the 6/18/25 office action that is not addressed below is withdrawn based on the amendments.
Previously, Group 2 was elected.
Since Group 2 was elected, claims 1 and 14-16 are drawn to non-elected groups.
Claims 1 and 14-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 4/28/25.
Previously the species of SEQ ID NO: 4, 5 and 6 were elected.
As recognized by the applicants, claims 9-11 do not read on the elected species.
Claims 9-11 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 4/28/25.
Claims to the elected species are rejected as set forth below. Any relevant art that was uncovered during the search for the elected species is cited herein in order to advance prosecution.
It is unclear if newly added claims 17-18 read on the elected species (see 112 rejection below). Although unclear, claims 17-18 have been included in the instant examination.
Claims 2-8, 12-13 and 17-18 are being examined.
Priority
The priority information is found in the filing receipt of 9/20/22.
Specification
The objection below is maintained from the previous office action.
The disclosure is objected to because of the following informalities:
37 CFR 1.821(d) recognizes that each occurrence of a sequence should include the corresponding sequence identifier. In the instant case, Tables 1-2 recite in numerous locations the sequence EEQAE but do not recite the corresponding sequence identifier (SEQ ID NO: 1).
Appropriate correction is required.
Response to Arguments – Specification Objection
Applicant's arguments filed 9/24/25 have been fully considered but they are not persuasive.
Although applicants argue that that the sequence identifier provided in the description of the sequence listing discloses sequence 1, 37 CFR 1.821(d) recognizes that each occurrence of a sequence should include the corresponding sequence identifier. The issue is not what is present in the sequence listing, the issue is that the sequence as recited in Tables 1 and 2 does not include the corresponding sequence identifier (i.e. “SEQ ID NO: 1”).
Claim Rejections - 35 USC § 112
The rejection below is a new rejection necessitated by amendment.
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 17-18 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.
Newly added claim 17 recites ‘the nucleic acid encoding the synthetic N-terminal extension consists essentially of the amino acid sequence of SEQ ID NO:1’. MPEP 2111.03 states that “the transitional phrase "consisting essentially of" limits the scope of a claim to the specified materials or steps "and those that do not materially affect the basic and novel characteristic(s)" of the claimed invention”. In the instant case, it is not clear which sequences fall within the scope of consist essentially of and what materials would or would not materially affect the basic and novel characteristic of the claimed invention. The instant specification does not appear to use the phrase ‘consists essentially of’ and it is unclear if such phrase includes new matter. It is unclear if the elected species reads on claim 17.
Newly added claim 18 recites ‘the nucleic acid encoding the synthetic N-terminal extension consists of the amino acid sequence of SEQ ID NO:1’. The claim expressly recites N-terminal extension which implies that more than the N-terminal extension is required. In fact, the specification describes N-terminal extension in relation to linkage to a N-terminal amino acid (page 8 lines 9-11 of the specification). However, the language ‘consists of’ is closed. As such, the claim appears to suggest linkage to an amino acid sequence (in relation to SEQ ID NO:1) as well as SEQ ID NO:1 itself (using closed language). As such, there is more than one reasonable interpretation of the claim. It is unclear if the language N-terminal extension allows for components in addition to SEQ ID NO:1.
Although unclear, claims 17-18 have been interpreted as including no new matter and since both claims recite ‘N-terminal extension’ the claims have been interpreted as allowing for components in addition to SEQ ID NO:1. MPEP 2111.03 III recites: For the purposes of searching for and applying prior art under 35 USC 102 and 103, absent a clear indication in the specification or claims of what the basic and novel characteristics actually are, "consisting essentially of" will be construed as equivalent to "comprising."
Claim Rejections - 35 USC § 101
Claims were previously rejected under 101. Since the claims have been amended and new claims added the rejection is updated to correspond to the instant claims.
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 2-4 and 17-18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon (product of nature) without significantly more. The claim(s) recite(s) peptides/compositions which correspond to products of nature (as discussed in detail below). This judicial exception is not integrated into a practical application because there is no additional elements that apply or use the judicial exception. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception as discussed below.
This 101 rejection is consistent with the most recent training provided by the office which will be referred to as 'guidance' (see MPEP 2106).
In comparison to the subject matter eligibility test as set forth in the guidance, claims 2-4 and 17-18 are drawn to nucleic acids/vectors. Thus the answer to step 1 is yes.
Byrum et al. (US 2008/0066199; ‘Byrum’) teach that nucleic acid of SEQ ID NO:40489 encodes for a soybean protein (section 0022). On page 28 of Byrum, the sequence listing section points to a web site that recites the sequence. Sequence Data for US20080066199 (retrieved from https://seqdata.uspto.gov/seqdetail?docId=US20080066199A1&publicationNo=20080066199&seqId=40489 on 6/3/2025, 2 pages) show that residues 178-192 are gaagaacaggcagaa which is instant SEQ ID NO:7. SEQ ID NO:40489 encodes for the peptide comprising EEQAERSGQMECKYYLRSGGCKF which comprises EEQAE (instant SEQ ID NO:1) and a cleavable moiety LR (cleavable by trypsin). In relation to prong one of step 2a of the guidance the answer is yes because the nucleic acid correspond to naturally occurring nucleic acids (i.e. products of nature which are a natural phenomenon).
In relation to prong two of step 2a, the instant claims are product claims and do not require any additional elements that apply the judicial exception in a manner that imposes a meaningful limit on the judicial exception. Thus the answer to prong two of step 2a is no.
The Myriad Supreme Court decision (Association for Molecular Pathology v. Myriad Genetics, 569 U.S. 12-398 (2013)) stated: “Myriad’s claims are not saved by the fact that isolating DNA from the human genome severs the chemical bonds that bind gene molecules together” (page 2 and 14). In the instant case, applicants’ claims would not be saved even if they are limited to specific fragments.
Claim 2 recites ‘synthetic’. Claim 2 is drawn to a nucleic acid. MPEP 2106.04(b) II recites “As the Supreme Court made clear, neither naturally occurring compositions of matter, nor synthetically created compositions that are structurally identical to the naturally occurring compositions, are patent eligible”. Whether or not the nucleic acid is synthesized naturally in nature or synthesized in some other fashion does not necessarily mean that the structure of the nucleic acid is any different. Further, MPEP 2106.04(b) II recites “a synthetic, artificial, or non-naturally occurring product such as a cloned organism or a human-made hybrid plant is not automatically eligible because it was created by human ingenuity or intervention” and refers to the key being “whether they possess markedly different characteristics from any naturally occurring counterpart”.
In relation to step 2b, claim 5 recites a vector. However, the generic recitation of vector does not require anything that is structurally different than the natural nucleic acids. The claims do not require any additional features that add significantly more to the exceptions.
Further, there is no evidence of any markedly different characteristic. Thus the answer to step 2b is no because there is not adequate evidence to conclude that the claims include significantly more than the judicial exception.
Response to Arguments – 101
Applicant's arguments filed 9/24/25 have been fully considered but they are not persuasive with respect to the rejection set forth above.
Although applicants argue that the objective is to increase expression of peptides, the instantly examined claims are nucleic acids not methods of expression.
Although applicants argue about example 3 and the use of TEV, all of the limitations of example 3 are not recited in instant claim 2. It is noted that only claims 2-4 and 17-18 are rejected under 101.
Although applicants argue about apparent benefits of certain expression strategies, the instantly examined claims are nucleic acids not methods of expression.
Although applicants argue that the claims have been amended and recite synthetic, claim 2 is drawn to a nucleic acid. MPEP 2106.04(b) II recites “As the Supreme Court made clear, neither naturally occurring compositions of matter, nor synthetically created compositions that are structurally identical to the naturally occurring compositions, are patent eligible”. Whether or not the nucleic acid is synthesized naturally in nature or synthesized in some other fashion does not necessarily mean that the structure of the nucleic acid is any different. Further, MPEP 2106.04(b) II recites “a synthetic, artificial, or non-naturally occurring product such as a cloned organism or a human-made hybrid plant is not automatically eligible because it was created by human ingenuity or intervention” and refers to the key being “whether they possess markedly different characteristics from any naturally occurring counterpart”.
Although applicants argue about codon optimized constructs, Byrum et al. (US 2008/0066199; ‘Byrum’) teach that nucleic acid of SEQ ID NO:40489 encodes for a soybean protein (section 0022). On page 28 of Byrum, the sequence listing section points to a web site that recites the sequence. Sequence Data for US20080066199 (retrieved from https://seqdata.uspto.gov/seqdetail?docId=US20080066199A1&publicationNo=20080066199&seqId=40489 on 6/3/2025, 2 pages) show that residues 178-192 are gaagaacaggcagaa which is instant SEQ ID NO:7 which is recited in claim 3.
Although applicants argue about pD912, instant claim 5 is not included in the 101 rejection.
Claim Rejections - 35 USC § 102
Claims were previously rejected under 102. Since the claims have been amended and new claims added the rejections are updated to correspond to the instant claims.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 2 and 17-18 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schellenberger et al. (US 2015/0037359 as cited with IDS 8/10/22; ‘Schellenberger’).
Schellenberger teach a DNA sequence and corresponding amino acid sequence in Table 29 (page 175). The nucleic acid encodes for EEQAE (first line of sequence) which further comprises RS (3rd line of sequence). Table 9 on page 100 recites known cleavage sites including trypsin with R/X.
In relation to claims 2 and 17-18, Schellenberger teach a DNA sequence and corresponding amino acid sequence in Table 29 (page 175) where the nucleic acid encodes for EEQAE (first line of sequence) which is instant SEQ ID NO:1. Further, the nucleic acid encodes for RS (3rd line of sequence) and Table 9 on page 100 recites known cleavage sites including trypsin with R/X. Claim 2 is drawn to a nucleic acid and has been amended to recite synthetic. Whether or not the nucleic acid is synthesized naturally in nature or synthesized in some other fashion does not necessarily mean that the structure of the nucleic acid is any different.
Claim(s) 2-4 and 17-18 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Byrum et al. (US 2008/0066199; ‘Bynum’) as evidenced by Sequence Data for US20080066199 (retrieved from https://seqdata.uspto.gov/seqdetail?docId=US20080066199A1&publicationNo=20080066199&seqId=40489 on 6/3/2025, 2 pages).
Byrum teach that nucleic acid of SEQ ID NO:40489 encodes for a soybean protein (section 0022). On page 28 of Byrum, the sequence listing section points to a web site that recites the sequence. Sequence Data for US20080066199 (retrieved from https://seqdata.uspto.gov/seqdetail?docId=US20080066199A1&publicationNo=20080066199&seqId=40489 on 6/3/2025, 2 pages) show that residues 178-192 are gaagaacaggcagaa which is instant SEQ ID NO:7. SEQ ID NO:40489 encodes for the peptide comprising EEQAERSGQMECKYYLRSGGCKF which comprises EEQAE (instant SEQ ID NO:1) and a cleavable moiety LR (cleavable by trypsin).
In relation to claims 2-4 and 17-18, Byrum teach nucleic acid of SEQ ID NO:40489 which comprises gaagaacaggcagaa (at residues 178-192) which is instant SEQ ID NO:7. SEQ ID NO:40489 encodes for the peptide comprising EEQAERSGQMECKYYLRSGGCKF which comprises EEQAE (instant SEQ ID NO:1) and a cleavable moiety LR (cleavable by trypsin). The nucleic acid sequence as set forth in Byrum is suitable to be used as a vector as recited in claim 4. Claim 2 is drawn to a nucleic acid and has been amended to recite synthetic. Whether or not the nucleic acid is synthesized naturally in nature or synthesized in some other fashion does not necessarily mean that the structure of the nucleic acid is any different.
Response to Arguments – 102
Applicant's arguments filed 9/24/25 have been fully considered but they are not persuasive with respect to the rejection set forth above.
Although applicants argue about a sequence in Table 31, the instant rejection is based on Table 29. Table 29 expressly teach the following (with spacing to identify the nucleic acid and corresponding amino acid):
ATG AAA AAC CCA GAG CAA GCA GAA GAA CAA GCT GAA GAA CAG
M K N P E Q A E E Q A E E Q
which encodes for EEQAE (instant SEQ ID NO:1).
Although applicants argue that there is no indication about an N-terminal extension, the office action states: “Schellenberger teach a DNA sequence and corresponding amino acid sequence in Table 29 (page 175). The nucleic acid encodes for EEQAE (first line of sequence) which further comprises RS (3rd line of sequence). Table 9 on page 100 recites known cleavage sites including trypsin with R/X.” The instant specification (page 8 lines 9-11) describes N-terminal extension in terms of being able to be removably linked. The known cleavage site discussed above is evidence that it can be removably linked.
Although applicants argue about the teachings of Schellenberger et al. in relation to the 102 rejection of claim 3, claim 3 is not rejected under 102 based on Schellenberger et al.
Although applicants argue that claim 2 recites an N-terminal extension, claim 2 is drawn to a nucleic acid and has been amended to recite synthetic. Whether or not the nucleic acid is synthesized naturally in nature or synthesized in some other fashion does not necessarily mean that the structure of the nucleic acid is any different. With respect to the extension, the instant specification (page 8 lines 9-11) describes N-terminal extension in terms of being able to be removably linked. As set forth in the previous and current rejection , Byrum teach SEQ ID NO:40489 and “SEQ ID NO:40489 encodes for the peptide comprising EEQAERSGQMECKYYLRSGGCKF which comprises EEQAE (instant SEQ ID NO:1) and a cleavable moiety LR (cleavable by trypsin)”. The known cleavage site discussed above is evidence that it can be removably linked.
Claim Rejections - 35 USC § 103
Claims were previously rejected under 103. Since the claims have been amended and new claims added the rejections are updated to correspond to the instant claims.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 2-4, 6-8, 12-13 and 17-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schellenberger et al. (US 2015/0037359 as cited with IDS 8/10/22; ‘Schellenberger’) in view of Kim et al. (WO 2019/143193 07-2019 as cited with the IDS of 8/10/22)
Kim et al. is not in the English language. The English language equivalent US 2020/0347111 (KimTranslation) will be referred to herein.
Schellenberger teach conjugate compositions comprising polypeptides (abstract). Schellenberger teach the inclusion of a helper sequence (section 0007 and claim 16). Schellenberger teach the inclusion of the helper sequence at the 5’ end of the polynucleotide encoding the polypeptide to enhance and facilitate the expression (section 0272 and section 0272 title on page 100). Schellenberger teach examples of helper sequences that comprise EEQAE (section 0007 line 27; Table 10 page 102 18th-22nd sequences for example; Table 29; Table 36 first 2 sequences; section 0495 and claim 16). Table 36 of Schellenberger recites the helper sequences which include the highest expression levels. In Table 29, Schellenberger recites that the DNA sequence encoding for EEQAE is GAAGAACAAGCTGAA. Schellenberger teach the inclusion of a cleavage sequence between the helper sequence and the polypeptide (section 0008). Schellenberger teach ENLYFQG as an exemplary cleavage sequence which is known as TEV (table 9 page 100). Schellenberger teach the use of plasmid expression vector for protein expression and recite that expression can be in bacteria or yeast and recite vectors such as pET (sections 0443-0444) and recognize expression in E. coli (sections 0078, 0440 and 0493). Schellenberger teach that the polypeptide can be GLP-1 (section 0282 and Table 12). Schellenberger teach that the gene can be codon optimized (sections 0441 and 0480) and in Tables 33-34 for example Schellenberger recites various codon sequences.
Schellenberger does not specifically recite liraglutide.
KimTranslation teach the production of target polypeptides and recognizes the use of N-terminal fusion partners to enhance yield (abstract). KimTranslation teach that the target polypeptide is GLP-1 or liraglutide (claim 13). KimTranslation teach liraglutide as an analog of GLP-1 and specifically recites SEQ ID NO: 341 (section 0138). KimTranslation teach that liraglutide is a known therapeutic agent for type 2 diabetes or obesity (section 0138).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of Schellenberger based on the specific teachings and suggestions of Schellenberger. Since Schellenberger teach conjugate compositions comprising polypeptides (abstract) which include a helper sequence (section 0007 and claim 16) and teach the inclusion of the helper sequence at the 5’ end of the polynucleotide encoding the polypeptide to enhance and facilitate the expression (section 0272 and section 0272 title on page 100) one would have been motivated to include a helper sequence. Since Schellenberger teach examples of helper sequences that comprise EEQAE (section 0007 line 27; Table 10 page 102 18th-22nd sequences for example; Table 29; Table 36 first 2 sequences; section 0495 and claim 16) and specifically teach such sequence as including the highest expression levels (Table 36) one would have been motivated to make constructs encoding for such sequence. In Table 29, Schellenberger recites that the DNA sequence encoding for EEQAE is GAAGAACAAGCTGAA. Further, Schellenberger teach that the gene can be codon optimized (sections 0441 and 0480) and in Tables 33-34 for example Schellenberger recites various codon sequences and recognize that GCT as an alternate to GCC and recognize GCT as occurring in the high expression group. Thus one would have been motivated to substitute GCT for GCC resulting in GAAGAACAAGCCGAA. Since Schellenberger teach the inclusion of a cleavage sequence between the helper sequence and the polypeptide (section 0008) and teach ENLYFQG as an exemplary cleavage sequence which is known as TEV (table 9 page 100) one would have been motivated to encode for and codon optimize such sequence in the construct. Since Schellenberger teach that the polypeptide can be GLP-1 (section 0282 and Table 12) and KimTranslation teach liraglutide as an analog of GLP-1 is a known therapeutic agent for type 2 diabetes or obesity (section 0138) one would have been motivated to encode for and codon optimize SEQ ID NO: 341 which is specifically recited (section 0138). Since Schellenberger teach the use of plasmid expression vectors for protein expression and recite that expression can be in bacteria or yeast and recite vectors such as pET (sections 0443-0444) and recognize expression in E. coli (sections 0078, 0440 and 0493) one would have been motivated to make vectors and use E. coli as a host cell. One would have had a reasonable expectation of success since methods of preparing nucleic acid sequences and vectors were known (Schellenberger examples).
In relation to claims 2 and 17-18, Schellenberger teach a DNA sequence and corresponding amino acid sequence in Table 29 (page 175) where the nucleic acid encodes for EEQAE (first line of sequence) which is instant SEQ ID NO:1. Further, the nucleic acid encodes for RS (2nd line of sequence) and Table 9 on page 100 recites known cleavage sites including trypsin with R/X. Claim 2 is drawn to a nucleic acid and has been amended to recite synthetic. Whether or not the nucleic acid is synthesized naturally in nature or synthesized in some other fashion does not necessarily mean that the structure of the nucleic acid is any different.
In relation to claim 3 and the gene sequence of claims 7-8, in Table 29, Schellenberger recites that the DNA sequence encoding for EEQAE is GAAGAACAAGCTGAA. Further, Schellenberger teach that the gene can be codon optimized (sections 0441 and 0480) and in Tables 33-34 for example Schellenberger recites various codon sequences and recognizes that GCT as an alternate to GCC and recognize GCT as occurring in the high expression group. Thus one would have been motivated to substitute GCT for GCC resulting in GAAGAACAAGCCGAA which is instant SEQ ID NO:4.
In relation to claims 4 and 7-8, Schellenberger teach the use of plasmid expression vectors for protein expression and recite that expression can be in bacteria or yeast and recite vectors such as pET (sections 0443-0444).
In relation to claim 6 and the TEV of claims 7-8, Schellenberger teach the inclusion of a cleavage sequence between the helper sequence and the polypeptide (section 0008) and teach ENLYFQG as an exemplary cleavage sequence which is known as TEV (table 9 page 100) so one would have been motivated to encode for and codon optimize such sequence.
In relation to claim peptide of claims 7-8, Schellenberger teach that the polypeptide can be GLP-1 (section 0282 and Table 12) and KimTranslation teach liraglutide as an analog of GLP-1 is a known therapeutic agent for type 2 diabetes or obesity so one would have been motivated to encode for and codon optimize SEQ ID NO: 341 which is specifically recited (section 0138).
In relation to claims 12-13, Schellenberger teach the use of plasmid expression vectors for protein expression and recite that expression can be in bacteria or yeast and recite vectors such as pET (sections 0443-0444) and recognize expression in E. coli (sections 0078, 0440 and 0493).
Claim(s) 2-8, 12-13 and 17-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schellenberger et al. (US 2015/0037359 as cited with IDS 8/10/22; ‘Schellenberger’) in view of Kim et al. (WO 2019/143193 07-2019 as cited with the IDS of 8/10/22) in view of Kurihara et al. (US 2017/0240941; ‘Kurihara’).
Kim et al. is not in the English language. The English language equivalent US 2020/0347111 (KimTranslation) will be referred to herein.
Schellenberger teach conjugate compositions comprising polypeptides (abstract). Schellenberger teach the inclusion of a helper sequence (section 0007 and claim 16). Schellenberger teach the inclusion of the helper sequence at the 5’ end of the polynucleotide encoding the polypeptide to enhance and facilitate the expression (section 0272 and section 0272 title on page 100). Schellenberger teach examples of helper sequences that comprise EEQAE (section 0007 line 27; Table 10 page 102 18th-22nd sequences for example; Table 29; Table 36 first 2 sequences; section 0495 and claim 16). Table 36 of Schellenberger recites the helper sequences which include the highest expression levels. In Table 29, Schellenberger recites that the DNA sequence encoding for EEQAE is GAAGAACAAGCTGAA. Schellenberger teach the inclusion of a cleavage sequence between the helper sequence and the polypeptide (section 0008). Schellenberger teach ENLYFQG as an exemplary cleavage sequence which is known as TEV (table 9 page 100). Schellenberger teach the use of plasmid expression vector for protein expression and recite that expression can be in bacteria or yeast and recite vectors such as pET (sections 0443-0444) and recognize expression in E. coli (sections 0078, 0440 and 0493). Schellenberger teach that the polypeptide can be GLP-1 (section 0282 and Table 12). Schellenberger teach that the gene can be codon optimized (sections 0441 and 0480) and in Tables 33-34 for example Schellenberger recites various codon sequences.
Schellenberger does not specifically recite liraglutide or pD912.
KimTranslation teach the production of target polypeptides and recognizes the use of N-terminal fusion partners to enhance yield (abstract). KimTranslation teach that the target polypeptide is GLP-1 or liraglutide (claim 13). KimTranslation teach liraglutide as an analog of GLP-1 and specifically recites SEQ ID NO: 341 (section 0138). KimTranslation teach that liraglutide is a known therapeutic agent for type 2 diabetes or obesity (section 0138).
Kurihara teach methods of producing a polypeptide (section 0044). Kurihara teach that known expression vectors include pET and pD912 (section 0062) and also recognizes the use of Pichia pastoris (sections 0012 and 0064).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of Schellenberger based on the specific teachings and suggestions of Schellenberger. Since Schellenberger teach conjugate compositions comprising polypeptides (abstract) which include a helper sequence (section 0007 and claim 16) and teach the inclusion of the helper sequence at the 5’ end of the polynucleotide encoding the polypeptide to enhance and facilitate the expression (section 0272 and section 0272 title on page 100) one would have been motivated to include a helper sequence. Since Schellenberger teach examples of helper sequences that comprise EEQAE (section 0007 line 27; Table 10 page 102 18th-22nd sequences for example; Table 29; Table 36 first 2 sequences; section 0495 and claim 16) and specifically teach such sequence as including the highest expression levels (Table 36) one would have been motivated to make constructs encoding for such sequence. In Table 29, Schellenberger recites that the DNA sequence encoding for EEQAE is GAAGAACAAGCTGAA. Further, Schellenberger teach that the gene can be codon optimized (sections 0441 and 0480) and in Tables 33-34 for example Schellenberger recites various codon sequences and recognize that GCT as an alternate to GCC and recognize GCT as occurring in the high expression group. Thus one would have been motivated to substitute GCT for GCC resulting in GAAGAACAAGCCGAA. Since Schellenberger teach the inclusion of a cleavage sequence between the helper sequence and the polypeptide (section 0008) and teach ENLYFQG as an exemplary cleavage sequence which is known as TEV (table 9 page 100) one would have been motivated to encode for and codon optimize such sequence in the construct. Since Schellenberger teach that the polypeptide can be GLP-1 (section 0282 and Table 12) and KimTranslation teach liraglutide as an analog of GLP-1 is a known therapeutic agent for type 2 diabetes or obesity (section 0138) one would have been motivated to encode for and codon optimize SEQ ID NO: 341 which is specifically recited (section 0138). Since Schellenberger teach the use of plasmid expression vectors for protein expression and recite that expression can be in bacteria or yeast and recite vectors such as pET (sections 0443-0444) and recognize expression in E. coli (sections 0078, 0440 and 0493) one would have been motivated to make vectors and use E. coli as a host cell. Schellenberger teach the use of plasmid expression vectors for protein expression and recite that expression can be in bacteria or yeast and recite vectors such as pET (sections 0443-0444). Since Kurihara teach methods of producing a polypeptide (section 0044) and teach that known expression vectors include pET and pD912 (section 0062) one would have been motivated to use the known pD912 vector. Since Kurihara recognizes the use of Pichia pastoris (sections 0012 and 0064) one would have been motivated to codon optimize for and use such expression system. One would have had a reasonable expectation of success since methods of preparing nucleic acid sequences and vectors were known (Schellenberger examples).
In relation to claims 2 and 17-18, Schellenberger teach a DNA sequence and corresponding amino acid sequence in Table 29 (page 175) where the nucleic acid encodes for EEQAE (first line of sequence) which is instant SEQ ID NO:1. Further, the nucleic acid encodes for RS (2nd line of sequence) and Table 9 on page 100 recites known cleavage sites including trypsin with R/X. Claim 2 is drawn to a nucleic acid and has been amended to recite synthetic. Whether or not the nucleic acid is synthesized naturally in nature or synthesized in some other fashion does not necessarily mean that the structure of the nucleic acid is any different.
In relation to claim 3 and the gene sequence of claims 7-8, in Table 29, Schellenberger recites that the DNA sequence encoding for EEQAE is GAAGAACAAGCTGAA. Further, Schellenberger teach that the gene can be codon optimized (sections 0441 and 0480) and in Tables 33-34 for example Schellenberger recites various codon sequences and recognizes that GCT as an alternate to GCC and recognize GCT as occurring in the high expression group. Thus one would have been motivated to substitute GCT for GCC resulting in GAAGAACAAGCCGAA which is instant SEQ ID NO:4.
In relation to claims 4 and 7-8, Schellenberger teach the use of plasmid expression vectors for protein expression and recite that expression can be in bacteria or yeast and recite vectors such as pET (sections 0443-0444).
In relation to claim 6 and the TEV of claims 7-8, Schellenberger teach the inclusion of a cleavage sequence between the helper sequence and the polypeptide (section 0008) and teach ENLYFQG as an exemplary cleavage sequence which is known as TEV (table 9 page 100) so one would have been motivated to encode for and codon optimize such sequence.
In relation to claim peptide of claims 7-8, Schellenberger teach that the polypeptide can be GLP-1 (section 0282 and Table 12) and KimTranslation teach liraglutide as an analog of GLP-1 is a known therapeutic agent for type 2 diabetes or obesity so one would have been motivated to encode for and codon optimize SEQ ID NO: 341 which is specifically recited (section 0138).
In relation to claims 12-13, Schellenberger teach the use of plasmid expression vectors for protein expression and recite that expression can be in bacteria or yeast and recite vectors such as pET (sections 0443-0444) and recognize expression in E. coli (sections 0078, 0440 and 0493). Kurihara teach that known expression vectors include pET and pD912 (section 0062) and also recognizes the use of Pichia pastoris (sections 0012 and 0064).
Response to Arguments – 103
Applicant's arguments filed 9/24/25 have been fully considered but they are not persuasive with respect to the rejection set forth above.
Although applicants argue that Schellenberger alone does not teach the claims, the 103 rejection are multiple reference 103 rejections and as such any single reference does not necessarily anticipate the claims.
Although applicants argue that in relation to claim 7 Schellenberger teach amino acid sequences that are longer than 5, instant claim 7 recites ‘comprising’ (line 1) which is open ended language allowing for the inclusion of additional components.
Although applicants argue that Schellenberger does not teach SEQ ID NO:4, the 103 rejections are multiple reference 103 rejections and as such any single reference does not necessarily anticipate the claims. In relation to claim 3 and the gene sequence of claims 7-8, in Table 29, Schellenberger recites that the DNA sequence encoding for EEQAE is GAAGAACAAGCTGAA. Further, Schellenberger teach that the gene can be codon optimized (sections 0441 and 0480) and in Tables 33-34 for example Schellenberger recites various codon sequences and recognizes that GCT as an alternate to GCC and recognize GCT as occurring in the high expression group. Thus one would have been motivated to substitute GCT for GCC resulting in GAAGAACAAGCCGAA which is instant SEQ ID NO:4.
Conclusion
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.
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RONALD T. NIEBAUER
Primary Examiner
Art Unit 1658
/RONALD T NIEBAUER/Examiner, Art Unit 1658