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 .
Priority
This application is a national stage entry under 35 U.S.C. 371 of PCT/EP2022/053425 (filed on 2/11/2022), which claims priority to EP2115696.8 (filed on 02/12/2021).
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 12/17/2025 is acknowledged. Claims 1-5 and 7-8 read on the elected group.
Upon reconsideration, the restriction requirement between Groups I and II and the species election for Genus (A) and Genus (B) as set forth in the Office action mailed on 9/17/2025 is hereby withdrawn. Therefore, claims 1-5, 7-8, 10, 11 and 13 are being examined. Restriction between Groups (I and II) and III is maintained. Claims 14-18, 20 and 29-32 are withdrawn from consideration pursuant to 37 CFR 1.140(b) as being drawn to nonelected Group III, there being no allowable generic or linking claim.
In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicants are advised that if any claim presented in a divisional application is anticipated by or includes all the limitations of , a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or non-statutory double patenting rejections over the claims of the instant application.
Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See, In re Ziegler, 443 F.2d 1221, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claim Status
Claims 1-5,7-8,10-11,13-18,20,29-32 are pending.
Claims 14-18,20,29-32 are withdrawn from consideration based on restriction election.
Claims 1-5,7-8,10-11, and 13 have been considered on the merits.
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 1-5,7-8,10-11, and 13 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 contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for 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.
MPEP § 2163, the analysis of whether the specification complies with the written description requirement calls for the examiner to compare the scope of the claim with the scope of the description to determine whether applicant has demonstrated possession of the claimed invention from the standpoint of one of skill in the art at the time the application was filed. For inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession.
Claim 8 is drawn to a secretion signal. Claim 8 covers a genus of molecules. The genus includes signal peptide sequence originating from KRE1 or SWP1 protein and comprising sequences of SEQ ID NO: 1 or SEQ ID NO:2, respectively, or a functional homolog thereof comprising at least 80 % sequence identity thereto. The issue at hand is the scope of “functional homologs that comprise at least 80% identity to SEQ ID NO: 1 or 2”.
The scope of the ‘functional homologs’ are defined by a structure : a signal peptide sequence having at least 80% identity to said sequence of SEQ ID NO: 1 or 2, as well as a function: serve as a functional homolog of SEQ ID NO: 1 or 2. Purely based on structure, the genus covers 320,000 sequences (80% identity to either of the 18 amino acid (AA) sequences of SEQ ID NOs: 1 or 2). Neither the specification nor the claims teach what specific function the homologs must retain (beyond, presumably ‘signal sequence’), or to what degree, or what portion of the sequence is responsible for said retained function.
For claims drawn to a genus, possession may be shown (for example) through (1) sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or (2) 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. A “representative number of species” means that the species which are adequately described are representative of the entire genus, and is an inverse function of the skill and knowledge in the art. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. 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. See, e.g., Eli Lilly. If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112(a).
In the instant case, regarding a representative number of species: the instant specification discloses full-length SEQ ID NO:1 and 2 (Examples). SEQ ID NO: 1 and 2 are 18 AA signal peptide sequences. The specification does not disclose any other embodiments which would be encompassed within the pending claim. The specification does not identify what changes, mutations, fragments, etc. could be made to SEQ ID NO: 1 or 2, and that would be encompassed by the structural limitations of claim 1, and would predictably result in the claimed function of secretion signal that increases yield of protein of interest in a host cell. As such, the instant specification does not provide a sufficient representative sampling of structures that are as little as 80% identical and that have as few as 14 AA out of a possible 18 AA present in SEQ ID NO: 1 or 2 that are capable of providing for said function as claimed.
Regarding identifying characteristics: Neither the specification nor the prior art establishes a structure-function relationship wherein the nucleic acid molecule encodes for secretion signal peptide of at least 18 AA having 80% identity to SEQ ID NO: 1 or 2, would be capable of functioning as claimed with any degree of predictability.
The prior art is unpredictable. Thus, the prior art cannot be relied upon for making up for the deficit of the instant specification with regard to a sufficient representative number of species that are as little as 80% identical and that have as few as 14 out of a possible 18 amino acids present in SEQ ID NO: 2 that provide for said function as claimed.
Accordingly, neither the specification nor the prior art establishes a known structure-function relationship wherein the genus of structures that are as little as 80% identical and that have as few as 14 out of a possible 18 amino acids present in SEQ ID NO: 1 or 2 are capable of providing for the function as claimed with any predictability. The prior art highlights the need to individually test mutations for function. In this case, the skilled artisan would not have reasonably concluded at the time of the invention that application was in possession of the invention as claimed.
Claim 1 is drawn to a nucleic acid molecule encoding a fusion protein comprising from N-terminus to C-terminus the secretion signal of claim 8 and a protein of interest. As claim 1 recites the nucleotide sequences that encode for the molecules of claim 8, the scope of claim 1 is even broader than claim 8, given the redundancy of the genetic code. As such, claim 1 is also drawn to a large genus of molecules. The genus includes nucleotide sequence encoding for the secretion peptide variations included in the limitations of claim 8, as discussed above. The issue at hand is the combinatorial variation of the nucleotide sequence based on the scope of claim 8 and signal peptide sequence that includes SEQ ID NO: 1 or 2 or a functional homolog that comprises at least 80% identity to SEQ ID NO 1 or 2.
In this instant case, Applicant has failed to provide disclosure of species which are representative of the full scope of the claimed invention. Applicants’ disclosure is limited to SEQ ID NO: 18 and 19 a nucleotide sequence that corresponds to SEQ ID NO 1 and 2, which only represents two of the many possibilities of the scope of claim 1. This limited disclosure is not considered to be representative of the full breadth of the genus, as claimed.
Applicants have also failed to disclose of relevant, identifying characteristics, such as structure or other physical or chemical properties, or functional characteristics coupled with known or disclosed structures. Accordingly, neither the specification nor the prior art establishes a known structure-function relationship wherein the genus of the nucleotide sequence encodes for the signal peptides of claim 8 or a functional homolog at least 80% identical of SEQ ID NO: 1 or 2 are capable of providing for the function as claimed with any predictability. The prior art highlights the need to individually test mutations for function. In this case, the skilled artisan would not have reasonably concluded at the time of the invention that application was in possession of the invention as claimed.
Claim 4 is drawn to the nucleic acid molecule of claim 1. Claim 4 covers a genus of molecules. The genus includes signal peptide sequence originating from a SWP1 protein comprises SEQ ID NO: 2 or 52 or a functional homolog thereof. The issue at hand is the scope of “functional homolog thereof”.
The scope of the “functional homologs” are defined by a structure : nucleic acid molecule with signal peptide sequence of SEQ ID NO: 2 or 52, as well as a function: serve as a functional homolog of SEQ ID NO: 2 or 52. Purely based on the structure, the genus covers at least 2018 sequences (for the 18 amino acid (AA) sequence of SEQ ID NO 2 or 52). Neither the specification nor the claims teach what specific function the homologs must retain, or to what degree, or what portion of the sequence is responsible for said retained function.
In this instant case, Applicant has failed to provide disclosure of species which are representative of the full scope of the claimed invention. Applicants’ disclosure is limited to SEQ ID NO: 18, a nucleotide sequence that corresponds to SEQ ID NO 2, which only represents two of the many possibilities of the scope of claim 4. This limited disclosure is not considered to be representative of the full breadth of the genus, as claimed.
Applicants have also failed to disclose of relevant, identifying characteristics, such as structure or other physical or chemical properties, or functional characteristics coupled with known or disclosed structures. Accordingly, neither the specification nor the prior art establishes a known structure-function relationship wherein the genus of the nucleotide sequence encodes for the signal peptides of claim 4 or a functional homolog of SEQ ID NO: 2 or 52 are capable of providing for the function as claimed with any predictability. The prior art highlights the need to individually test mutations for function. In this case, the skilled artisan would not have reasonably concluded at the time of the invention that application was in possession of the invention as claimed.
Claim 5 is drawn to the nucleic acid molecule of claim 1. Claim 5 covers a genus of molecules. The genus includes MFα pro-sequence comprising (i) any one of SEQ ID NO 3,53, or 74-90 or functional homolog thereof. The issue at hand is the scope of “functional homolog thereof”.
The scope of the “functional homologs” are defined by a structure : nucleic acid molecule with MFα of any sequence of SEQ ID NO: 3, 53, or 74-80, as well as a function: serve as a functional homolog of SEQ ID NO: 3,53, or 74-80. Purely based on the structure, the genus covers at least 2066 sequences (for the 66 amino acid (AA) sequence of SEQ ID NO 3,53 or 74). Neither the specification nor the claims teach what specific function the homologs must retain, or to what degree, or what portion of the sequence is responsible for said retained function.
In this instant case, Applicant has failed to provide disclosure of species which are representative of the full scope of the claimed invention. Applicants’ disclosure is limited to SEQ ID NO: 20, a nucleotide sequence that corresponds to SEQ ID NO 3, which only represents two of the many possibilities of the scope of claim 5. This limited disclosure is not considered to be representative of the full breadth of the genus, as claimed.
Applicants have also failed to disclose of relevant, identifying characteristics, such as structure or other physical or chemical properties, or functional characteristics coupled with known or disclosed structures. Accordingly, neither the specification nor the prior art establishes a known structure-function relationship wherein the genus of the nucleotide sequence encodes for the signal peptides of claim 5 or a functional homolog of SEQ ID NO: 3,53, or 74-80 are capable of providing for the function as claimed with any predictability. The prior art highlights the need to individually test mutations for function. In this case, the skilled artisan would not have reasonably concluded at the time of the invention that application was in possession of the invention as claimed.
Claims 1-3,7,10-11, and 13 are included in the rejection because they depend from, at least, claim 1.
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 3 and 4 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.
The limitations of claims 3 and 4 include those of claim 1 which is dependent on 8. Claim 8 recites secretion signal comprising (1)….(II) a signal peptide sequence originating from a KRE1 protein or a signal peptide sequence originating from a SWP1 protein, wherein the signal peptide sequence originating from a KRE1 protein comprises SEQ ID NO: 1, or a functional homolog thereof comprising at least 80% sequence identity to SEQ ID NO: 1, and wherein the signal peptide sequence originating from a SWP1 protein comprises SEQ ID NO: 2, or a functional homolog thereof comprising at least 80% sequence identity thereto.
Claims 3 and 4 have a broader scope that that of claims 1/8, because claims 3 and 4 do not require the sequences to have at least 80% sequence identity to SEQ ID NO: 1 or 2 (KRE1 or SWP1). Due to the broader scope of nucleic acids covered by claims 3 and 4, the metes and bounds of claims 3 and 4 are unclear (unclear if they are limited to the narrower scope imposed by claim 1, or if they cover the fuller scope permitted by claims 3 and 4) This is especially true because the metes and bounds of functional homolog for claim 8 and therefore claim 1 has not been established by the Applicant. Applicant has also failed to disclose the metes and bounds of functional homolog of claim 3 and 4.
Therefore, claims 3 and 4 are rejected as being indefinite.
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 1-5,7,10-11, and 13 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 1 refers to the polypeptide of claim 8. Technically this makes claim 1 dependent on a later claim, and 35 U.S.C. 112(d) requires that a claim further limit a previous claim. It would be remedial to rewrite claims 1-5,7-8,10-11, and 13 as claims 33-42, respectively.
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 § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 8 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gasser et al (US 2017/0029827 A1).
Gasser et al discloses a method of expressing a protein of interest (POI) from a host cell. It is particularly drawn to improving the host cells’ capacity to express and or secrete a POI and use of the host cell for protein expression. More specifically it is drawn to culturing cells produce desired molecules for medical purposes or food products (See, Abstract). The invention is based on the findings of polynucleotide sequences whose over expression led to an increase in the yield of POI ( See, ¶0026).
Regarding claim 8, Gasser et al identified several helper proteins that can be used to increase POI yield, including helper protein 2 (HP2), which is SEQ ID NO 1 (amino acid sequence), encoded by SEQ ID 13 (polynucleotide sequence) (See, ¶0030 and Figure 1). SEQ ID NO: 1 and 13 of Gasser are 100% aligned with SEQ ID 1 and 19 of the instant application, respectively ( See, ¶0031) (See alignment in appendix). One embodiment of Gasser et al provides an isolated polynucleotide sequence which encodes a polypeptide sequence comprising SEQ ID NO 1 (See, ¶0032-0034). This reads on a secretion signal peptide sequence originating from KRE1 protein comprises SEQ ID NO:1 of claim 8.
Therefore claim 8 is anticipated by Gasser et al.
Claim Rejections - 35 USC § 103
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 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.
Claims 1-3,7,10,11,13 are rejected under 35 U.S.C. 103 as being unpatentable over Gasser et al as applied to claim 8 above, and further in view of Singh et al (Nucleic Acid Research,1984).
The teachings of Gasser et al are set forth above.
Regarding claim 1, Gasser et al teaches polynucleotides encoding the helper proteins and their individual or combined use to increase POI yield (See, ¶0031). The polynucleotides encoding the helper proteins can be introduced into a host cell or, if already existing in a cell, manipulated in a way such that they are over expressed (See, ¶0031). Gasser et al identified several helper proteins that can be used to increase POI yield, including helper protein 2 (HP2), which is SEQ ID NO 1 (amino acid sequence), encoded by SEQ ID 13 (polynucleotide sequence) (See, ¶0030 and Figure 1). SEQ ID NO: 1 and 13 of Gasser are 100% aligned with SEQ ID 1 and 19 of the instant application, respectively ( See, ¶0031). Finally, Gasser et al discloses use of the polynucleotides encoding the helper proteins for increasing POI yield, such that the nucleotide sequence encoding for the POI is combined within a cell with polynucleotides encoding the helper proteins, such that the cell co-expresses the POI and the helper protein (See, ¶0225).
While Gasser et al teaches modifying cells to contain polynucleotides encoding for both the POI and the helper protein, Gasser et al does not teach nucleic acid molecule or polynucleotide sequences that encodes for a fusion protein that includes both the helper protein (i.e. secretion signal peptide) and the protein of interest (POI).
However, Gasser et al describes HP2 as a helper protein, it is a secretion signal peptide, and as of the effective filing date it was known that fusing a POI with a secretion signal peptide will improve the secretion of the POI from the host cell. In support, see Singh et al:
Singh et al teaches that the MFα1 promoter and α-factor from Saccharomyces cerevisiae can direct synthesis and secretion of human leukocyte interferon D (IFN-α1) and have determined the processing of a natural α-factor prepro-IFN-α1 fusion protein (See, p8928 paragraph 1). Singh et al details a 1230 bp DNA fragment that contains MFα1 (secretion signal) and sequence coding for prepro-αfactor fused with modified IFN-α1 (POI) (See, p8930 paragraph 4, Figure 1 p8931). Singh et al teaches that the interferon was purified from growth medium of the yeast cell that was introduced with the plasmid containing the described DNA fragment with a plasmid (See, 8932). Singh et al concluded that the use of secretion signal peptide MFα1 can efficiently direct export of a heterologous protein, thus allows for protein of interest to be exported from yeast (See, p8937 paragraph 3).
Therefore, given that the HP2 is to serve as a secretion signal, it would have been obvious to have modified the method of Gasser et al to make the polynucleotide sequence of HP2 to include a POI and encode a fusion protein. This is achieved by constructing the nucleotide sequences in such a way that they would encode a fusion protein. One skilled in the art would have had a reasonable expectation of successfully creating this polynucleotide sequence encoding a fusion protein of a secretion signal and POI because Singh et al has described the construction and effective use in exporting protein of interest from a host (yeast) cell.
Regarding claim 2, following the discussion above about claim1, Gasser et al discloses an embodiment of the invention used in example 7, that showed an increase in yield of at least 20% up to 140%, of the POI (SDZ-Fab or HyHEL-Fab) in a recombinant cell engineered to overexpress helper protein (HP2 – SEQ ID NO 1) for manufacturing the POI (See, ¶0046-0047). This reads on a protein of interest recited in the claim 1 and on wherein the secretion signal increases secretion of said protein of interest from eukaryotic host cell…of claim 2.
Regarding claim 3, following the discussion above of claim 1, Gasser et al further discloses that the present invention provides an isolated polypeptide comprising the polypeptide sequence of any one of SEQ ID NO 1-9 or 162 or functional homologues thereof (See, ¶0034); SEQ ID NO 1 has 100% alignment with SEQ ID NO 1 of instant application (See, Appendix). This reads on wherein the signal peptide sequence originating from KRE1 protein comprises of SEQ ID NO: 1.
Regarding claim 7, following the discussion above of claim 1, Gasser et al discloses that the protein of interest (POI) refers to a protein that is produced by means of recombinant technology in a host cell. Further disclosed that the POI is usually a eukaryotic or prokaryotic polypeptide, variant or derivative thereof (See, ¶0296). Gasser et al further discloses that the POI can be a food additive (¶0297), an enzyme (¶0303), and a therapeutic protein (¶0304). The therapeutic protein may be not limited to a protein suitable as a biopharmaceutical, such as an antibody, antibody fragment, growth factor, hormone, enzyme, or vaccine (See, ¶0304). Gasser et al discloses that the POI is a mammalian polypeptide or human polypeptide, such as any polypeptide, protein, protein variant, fusion protein, and or fragment, which may be administered to a mammal (See, ¶0307). POI can also be an antigen binding fragment, such as an antibody, Fv, single-chain Fv (scFv), Fab, Fab’, F(ab’)2, and single domain antibody (sdAb) (See, ¶0307). This reads on wherein the POI is selected from the group consisting of Fab, scFv, therapeutic protein, or a food additive.
Regarding claim 10, following the discussion above of claim 1, Gasser et al discloses that the present invention provides a recombinant host cell for manufacturing a protein of interest, wherein the host cell is engineered to overexpress a polynucleotide encoding a help protein having an amino acid sequence of SEQ ID NO 1 or a functional homolog there of (See. ¶0036). This reads on, a recombinant eukaryotic host cell comprising the nucleic acid molecule of claim 1.
Regarding claim 11, following the discussion above of claim 10, Gasser et al discloses that a “host cell” refers to a cell which is capable of protein expression and optionally protein secretion, such as prokaryotic cells, eukaryotic cells, including yeast cells. Further disclosed is a list of yeast cells that is not limited to but includes, Saccharomyces cerevisiae, Saccharomyces kluyveri, Komagataella phaffii, Kluyveromyces lactis, Yarrowia lipolytica, and Pichia methanolica (See, ¶0244-0250). This reads on wherein the host cell consists of a fungal or yeast host cell.
Regarding claim 13, following the discussion above of claim 10, Gasser et al discloses that the present invention provides a recombinant host cell for manufacturing a protein of interest, wherein the host cell is engineered to overexpress a polynucleotide encoding a help protein having an amino acid sequence of SEQ ID NO 1 or a functional homolog there of (See. ¶0036). This reads on, wherein the host cell is engineered to overexpress one or more components of a signal recognition particle.
Therefore, claims 1-3,7,10,11,13 are rendered obvious by Gasser et al in view of Singh et al.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Gasser et al and Singh et al as applied to claims 1-3,7,10,11,13 above, and further in view of Sahara et al (US 2007/0117186 A1; as cited in the IDS filed 8/9/2023).
The teachings of Gasser et al and Singh et al are set forth above.
Regarding claim 4,following the discussion above of claim 1, Gasser et al teaches an embodiment of the invention, that provides an isolated polynucleotide sequence which encodes a polypeptide sequence of SEQ ID NO 1 or functional homolog (See, ¶0032-0034). This corresponds or aligns to SEQ ID NO 1 of the instant application.
Gasser et al does not teach a nucleic acid molecule encoding for signal peptide sequence originating from a SWP1 protein comprises SEQ ID NO: 2 or 52, or a functional homolog thereof.
Sahara et al discloses the identification of secretory signal peptides exhibiting higher secretion efficiency than conventional secretory signal peptides within the Saccharomyces cerevisiae genome (See, Abstract). Sahara et al teaches a DNA encoding a secretory signal peptide with the identifying gene encoding a protein containing the secretory signal peptide derived from Saccharomyces cerevisiae (See, ¶0051). The genes were selected from Saccharomyces cerevisiae genomic database and based on analysis, the gene regions encoding secretory signal peptides are extracted from the database using various prediction programs (See, ¶0051). In example 4 of Sahara et al , the secretion ability of secretory signal peptide was evaluated (See, ¶0157-163). Table 4 shows all the genes tested for their ability to secrete signal peptide and among those are KRE1 (YNL322c) and SWP1(YMR149w) (SEQ ID NO: 743), thus indicating that both of these variants have the capacity of producing secretion. While the SEQ ID NO: 743 does not align with SEQ ID NO 2 or 52 of the instant application or 80% thereof; the SWP1 of Sahara et al would be a functional homolog of the SWP1 of the instant application (it is emphasized claim 4 does not clearly require the limitation of at least 80% identity to SEQ ID NO: 2).
The use of the SWP1 of Saraha et al (having SEQ ID NO: 743), i.e. the functional homolog, is considered prima facie obvious. Given that both Gasser et al and Sahara et al teach suitable nucleotide encoding for peptides for POI yield, there was a reasonable expectation that they would work equivalently. Substitution of one element for another known in the field, wherein the result of the substitution would have been predictable, is considered to be obvious. See KSR International Co. v Teleflex Inc 82 USPQ2d 1385 (US 2007) at page 1395.
Therefore, claims 4 are rendered obvious by Gasser et al, Singh et al, and in further view of Sahara et al.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Gasser et al and Singh et al as applied to claims 1-3,7,10,11,13 above, and further in view of Stevens et al (WO 2019/222633 A1).
The teachings of Gasser et al and Singh et al are set forth above.
Gasser et al teaches that the POI may be linked with a leader sequence which causes secretion of the POI from the host cell. It is taught that the leader sequence may originate from yeast source, such as α-factor such as mating factor α (MFα) of Saccharomyces cerevisiae (See, ¶0317) Gasser et al also teaches that the secretion leader sequence can be fused to the nucleotide sequence encoding the POI and alternatively recombinant nucleotide sequence and the recombinant nucleotide sequence encoding a helper protein can be present in the same plasmid or cell, as single copies or multiple (See, ¶0318-0319). Gasser et al further teaches that the selection of the appropriate secretion leader sequence is apparent to a skilled person (See, ¶0317)
Gasser et al does not teach a sequence for MFα or MFα pro-sequence (SEQ ID NO: 3,53, or 74-80).
Stevens et al teaches recombinant strains and methods of improving secretion and productivity of recombinantly expressed proteins in yeast strains (See, ¶0082). Stevens et al teaches methods for producing a recombinant protein, for modifying protein by knocking out a gene, and for strain optimization for enhancing the secretion of proteins or metabolites from cells.
Stevens et al teaches SEQ ID NO 106; which has a 100% alignment to SEQ ID NO 3 in the instant application (See, Appendix). Used in example 6, where Stevens et al tests secretion efficacy for polypeptides in each comprising a different secretion signal (See, ¶00145). Strains recombinantly expressing alpha mating factor 1 (sc) (MFα1(sc)) and the results indicate that the deletion of the sec72 gene improves secretion for polypeptides comprising non-MFα1(sc) signal peptides (See, ¶00145-00146 and Figure 7).
Given that Gasser et al teaches the use of a MFα linked to a POI which causes secretions and Stevens et al teaches the use of MFα1(sc) to cause secretions, there is a reasonable expectation that they would work equivalently. Gasser et al provides motivations to use a preferred sequence for the use of the MFα as a leader sequence for secretion. This conclusion of obviousness is based on teaching suggestion motivation rationale. One would have had a reasonable expectation of success combining the leader sequence and nucleic acid molecule of Gasser et al with the teachings of the sequence for MFα1(sc) of Stevens et al.
Therefore, claim 5 is rendered obvious over Gasser et al in and Sahara et al, in further view of Stevens et al.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3,7-8, and 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 6 of U.S. Patent No. 10,865,416 B2.
Regarding claim 1-3,8 and 10, the patented claim 1 recites, a method of manufacturing a heterologous protein of interest in an isolated host cell comprising : providing an isolated host cell engineered to overexpress a polynucleotide encoding a helper protein having the amino acid sequence as shown in SEQ ID NO : 1 or a functional homologue thereof… wherein the heterologous protein of interest and the helper protein are different proteins , and wherein the yield of the heterologous protein of interest produced by the isolated host cell is increased as compared to a corresponding isolated host cell that does not overexpress the polynucleotide encoding the helper protein or the functional homologue….
Although the claims at issue are not identical, they are not patentably distinct from each other because patent claim 1 recites the polynucleotide encoding the helper protein with SEQ ID NO:1 (same as above and alignment in appendix), which reads on limitations of instant claims 1,3, and 8. Patent claim 1 also recites that the yield of the POI is increased compared to corresponding isolated host cell, which reads on the limitations of claim 2. Patent claim 1 also recites that this is all integrated into a host cell, which reads on the limitations of claim 10. Therefore, patent claim 1 renders instant claims 1-3, 8 and 10 obvious as taught in Gasser et al.
Regrading claim 7, following the discussion above, patent claim 6 recites, the method of claim 1, wherein the heterologous protein of interest is an enzyme, therapeutic protein, a food additive or a feed additive, or an antibody or an antibody fragment.
Although the claims at issue are not identical, they are not patentably distinct from each other because patent claim 6 recites the protein of interests that read on the limitations of instant claim 7. Therefore, patent claim 6 renders instant claim 7 as obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Caroline M Lara whose telephone number is (571)272-4262. The examiner can normally be reached 7:00 to 3:00pm M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CAROLINE M LARA/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633
APPENDIX
SEQUENCE ALIGNMENTS
RE: US 2017/0029827 A1
Query (instant SEQ ID NO: 1) vs Subject (referenced SEQ ID NO: 1)
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241
905
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Query (instant SEQ ID NO: 19) vs Subject (referenced SEQ ID NO: 13)
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258
907
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RE: WO 2019/222633 A1
Query (instant SEQ ID NO: 3) vs Subject (referenced SEQ ID NO: 106)
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278
674
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