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
Applicant’s election without traverse of Group I in the reply filed on 07/24/2026 is acknowledged.
Claims 1, 2, 10, 15-27, 29, 31, 35, and 36 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 07/24/2026.
Status of Claims
The amendment filed on 07/24/2026 amended claims 1-2, 4, 9, 10, 12, 16, 17, 19, 23-27, 29, 31, 35, and 36. Claims 3, 6-8, 11, 13-15, 18, 20-22, 28, 30, 32-34, and 38 were previously cancelled in the amendment filed 10/07/2024. Claims 1, 2, 4, 5, 9, 10, 12, 16, 17, 19, 23-27, 29, 31, and 35-37 are pending. Claims 1, 2, 10, 15-27, 29, 31, 35, and 36 are withdrawn as directed to a non-elected invention. Claims 4, 5, 9, 12, 16, 17, 19, 23-24, and 37 will be examined on the merits.
Priority
Provisional application 63/240,615 is acknowledged as disclosing the claimed invention and the effective filing date is 09/03/2021.
Information Disclosure Statement
The Information Disclosure Statements filed on 08/19/2024 and 07/24/2026 have been considered. Signed copies are enclosed.
The information disclosure statement filed 01/26/2026 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered. No copy of Cite No. 2 or 3 was provided.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
The replacement specification provided 07/24/2026 sufficiently discloses the SEQ ID NOs for the sequences listed in the instant specification. Therefore, the objection to the specification issued 05/26/2026 is withdrawn.
Claim Objections
Claims 4, 9, 12, objected to because of the following informalities: Claim 4 recites "C-terminus" and "N-terminus" in lines 13-15. Claim 9 recites "carboxyl terminus" and "amino terminus" in lines 2-4. Claim 12 recites "carboxyl terminus" and "amino terminus" in lines 3-5,14, and 16. Claim 37 recites "C-terminal or N terminal end" in lines 4-5. While “C-terminus” and “carboxyl terminus” are known equivalents in the art, as are “N- terminus” and “amino terminus”, consistency across the claims would improve claim clarity.
Claim 23 recites “INF-apha2”. Examiner cannot find a protein abbreviated as this. Examiner suggests that this is a typo for IFN-alpha 2, a common abbreviation for interferon α-2, as previously listed in the claim. Similarly, INF-gamma is interpreted as IFNγ, although this is not also listed in the claim. Applicant is asked to carefully review for typos, and/or provide the protein meant by the “INF”s.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claim 16 is 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 16 recites the limitation "the recombinant expression unit" in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 16 depends from claim 4, which does not recite a recombinant expression unit. The only claim that does recite a recombinant expression unit is claim 12; Examiner suggests amending claim 16 to be dependent on claim 12 to overcome this rejection.
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.
Claims 4, 5, 9, 16, 17, 23, and 24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Vasami et al., Journal of Applied Phycology (2020) 32:2889–2902.
The instant claims are drawn to a recombinant cyanobacterial host cell comprising a (αβ)3-CpcG heterohexameric phycocyanin disc, wherein the disc comprises three dimers comprising a CpcA and a CpcB linked together by a CpcG, wherein a first protein of interest (POI) and a second POI are expressed attached to one of CpcA, CpcB, or CpcG, and the two POIs are attached to different subunits.
Vasami et al. teach expression of a CpcB-PHLS fusion protein and a CpcA-GPPS fusion protein, with the POIs attached to the C-terminus of the Cpc proteins. Vasami teaches that these fusion proteins are able to self-assemble into phycocyanin subunits (heterohexameric discs), and a 27kb band can be seen in Figures 3A and 3B, indicating cpcG, which is expressed by Synechocystis, is part of the phycocyanin discs. Therefore, Vasami et al. teach a (αβ)3-CpcG heterohexameric disc with CpcA linked to GPPS and CpcB linked to PHLS, teaching instant claims 4, 5, and 9, which require the two proteins of interest to be linked to the N- or C-terminus of CpcA and CpcB. Vasami et al. also teach that these fusion proteins are controlled by the cpc promotor (see Figure 1D-F) and that they are expressed in a single celled cyanobacteria, Synechocystis sp. PCC 6803, teaching claims 16 and 17. The PHLS protein of Vasami et al. is a β-phellandrene synthase, and the GPPS protein of Vasami et al. is a geranyl diphosphate synthase, thus teaching claim 23. Finally, Vasami et al. teach a culture of this cyanobacterial host cell, teaching claim 24, in the methods section (see page 2891, paragraph 4, first line, “liquid culture”) and in the experiments throughout the whole document. Therefore, Vasami et al. anticipate instant claims 4, 5, 9, 16, 17, 23, and 24.
Claims 4, 16, 17, and 24 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Gao et al., Plant Physiology (2016) 172:1451–1464.
The instant claims are drawn to a recombinant cyanobacterial host cell comprising a (αβ)3-CpcG heterohexameric phycocyanin disc, wherein the disc comprises three dimers comprising a CpcA and a CpcB linked together by a CpcG, wherein a protein of interest (POI) is fused to the N- or C-terminus of CpcG.
Gao et al. teach YFP attached to the C-terminal end of CpcG, which serves as a linker in the phycobiliosomes that complex into photosystem I and further supercomplex into an NDH-1L-PSI supercomplex. Gao et al. show that CpcG still functions as part of that supercomplex, which still assembles, with the addition of a YFP on the C-terminal (see abstract, Figure S2, whole doc). Therefore, CpcG-YFP will still form (αβ)3-CpcG heterohexameric phycocyanin discs, which are part of the supercomplex studied in Gao et al. As such, Gao et al. teach a protein of interest (YFP) linked to the C-terminal end of a CpcG, and the production of (αβ)3-CpcG heterohexameric phycocyanin discs comprising CpcA, CpcB, CpcG, and the POI, thereby teaching instant claim 4. Gao et al. teach this in Synechocystis sp. strain PCC 6803, thereby teaching instant claim 17, and that the CpcG-YFP protein is under control of its native promotor (see Figure S2), teaching instant claim 16. Gao et al. teach cultures of this organism in the experiments and methods (see specifically, “Culture Conditions” heading on page 1460), teaching instant claim 24. Therefore, Gao et al. anticipates claims 4, 16, 17, and 24.
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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) 4, 5, 9, 12, 16, 17, 23, and 24, are is/are rejected under 35 U.S.C. 103 as being unpatentable over Vasami et al. in view of Gao et al.
The instant claims are drawn to a recombinant cyanobacterial host cell described in the above examples, as well as a cyanobacterial host cell comprising a (αβ)3-CpcG heterohexameric phycocyanin disc, wherein the disc comprises three dimers comprising a CpcA and a CpcB linked together by a CpcG, wherein a protein of interest (POI) is fused to the N- or C-terminus of CpcG, and a second POI is fused to the N- or C-terminus of CpcA or CpcB, with an optional cleavage site located between the Cpc protein and the POI.
Vasami et al. teach expression of a CpcB-PHLS fusion protein and a CpcA-GPPS fusion protein, with the POIs attached to the C-terminus of the Cpc proteins. Vasami teaches that these fusion proteins are able to self-assemble into phycocyanin subunits (heterohexameric discs), and a 27kb band can be seen in Figures 3A and 3B, indicating CpcG, which is expressed by Synechocystis (see Gao et al.), is part of the phycocyanin discs. Therefore, Vasami et al. teach a (αβ)3-CpcG heterohexameric disc with CpcA linked to GPPS and CpcB linked to PHLS, teaching instant claims 4, 5, and 9, which require the two proteins of interest to be linked to the N- or C-terminus of CpcA and CpcB. Vasami et al. also teach that these fusion proteins are controlled by the cpc promotor (see Figure 1D-F) and that they are expressed in a single celled cyanobacteria, Synechocystis sp. PCC 6803, teaching claims 16 and 17. The PHLS protein of Vasami et al. is a β-phellandrene synthase, and the GPPS protein of Vasami et al. is a geranyl diphosphate synthase, thus teaching claim 23. Finally, Vasami et al. teach a culture of this cyanobacterial host cell, teaching claim 24, in the methods section (see page 2891, paragraph 4, section “Growth conditions”) and in the experiments throughout the whole document.
Vasami et al. do not teach a (αβ)3-CpcG heterohexameric phycocyanin disc wherein the two proteins of interest are attached to CpcB and CpcG or CpcA and CpcG, as in instant claim 12. However, Gao et al. teach YFP attached to the C-terminal end of CpcG, which serves as a linker in the phycobiliosomes that complex into photosystem I and further supercomplex into an NDH-1L-PSI supercomplex. Gao et al. show that CpcG still functions as part of that supercomplex, which still assembles, with the addition of a YFP on the C-terminal (see abstract, Figure S2, whole doc). Therefore, CpcG with a C-terminal extension will still form (αβ)3-CpcG heterohexameric phycocyanin discs, which are part of the supercomplex studied in Gao et al. Gao et al. teach this in Synechocystis sp. strain PCC 6803, as in instant claim 17 and as in Vasami et al. Gao et al. also teach cultures of this organism in the experiments and methods (see specifically, “Culture Conditions” heading on page 1460), teaching instant claim 24.
It would be obvious to one of ordinary skill in the art that the proteins PHLS and GPPS, interchangeably linked to CpcA and CpcB in Vasami et al., could also be interchangeably linked to CpcG in view of Gao et al. Together, Vasami et al. and Gao et al. teach that extension of the C-terminus of each of the proteins that form the (αβ)3-CpcG heterohexameric disc of phycocyanin by a POI does not affect the ability of the protein to assemble into said disc. Therefore, one of ordinary skill in the art would have reasonable expectation of success when attaching a POI to the C-terminus of CpcA, CpcB, or CpcG. One would additionally expect that the disc would still assemble with proteins expressed on multiple components, because they assemble with two POIs on CpcA and CpcB, as seen in Vasami et al. Therefore, one of ordinary skill in the art would append a POI onto any two of CpcA, CpcB, and CpcG and have reasonable expectation that the (αβ)3-CpcG heterohexameric disc would still form. One would be motivated to express proteins of interest on any two of these proteins in order to express two different POIs on the same disc, allowing for heterologous production of recombinant proteins.
Finally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that a claim would have been obvious if the substitution of one known element for another yields predictable results to one of ordinary skill in the art. It would be obvious to apply a known element (a POI appended to the C-terminus of CpcG, taught by Gao et al.) for another (a POI appended to the C-terminus of either CpcA or CpcB, taught by Vasami et al.) to be used in a known method in the art to yield predictable results (all three elements CpcA, CpcB, and CpcG can have a POI attached to their C-terminus and still assemble into the heterohexameric discs, as recited above). Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary. Therefore, the combination of Vasami et al. and Gao et al. renders instant claims 4, 5, 9, 12, 16, 17, 23, and 24 obvious.
Claim(s) 4, 5, 9, 16, 17, 23, 24, and 37 are is/are rejected under 35 U.S.C. 103 as being unpatentable over Vasami et al. in view of Chakdar et al.
The instant claims are drawn to a recombinant cyanobacterial host cell comprising a (αβ)3-CpcG heterohexameric phycocyanin disc, wherein the disc comprises three dimers comprising a CpcA and a CpcB linked together by a CpcG, wherein a first protein of interest (POI) and a second POI are expressed attached to one of CpcA, CpcB, or CpcG, and the two POIs are attached to different subunits.
The teachings of Vasami et al. are recited above. However, Vasami et al. do not explicitly teach a disc preparation at least 90% pure. However, methods of purification of phycocyanin subunits are known in the art, as reviewed in Chakdar et al., Section 4.4, pages 59-62. Chakdar et al. review several different purification methods and their outcomes. Purification protocol for different cyanobacterial species have different parameters and varying success levels. Chakdar et al. disclose purity ratios of up to 5.59 in this section and in Table 4.1, indicating that high levels of purity can be achieved. One would be motivated to have pure extracts of the discs of Vasami et al. in order to isolate the proteins produced by the cyanobacteria in Vasami et al. It would be obvious to one of ordinary skill in this art to use any method known in the art, such as those presented in Chakdar et al., and optimize said method in order to achieve desired purity. KSR International Co. v. Teleflex Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007), discloses that if a method is “obvious to try”, it is not patentable over the prior art. MPEP § 2144.05(II) recites that routine optimization is “obvious to try”, and therefore supported by said rational. No specific method of purification is used in the specification or recited in the claims to reach this 90% pure preparation. Therefore, any method known in the art can be used to do so. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary, and claim 37 is obvious in view of Vasami et al. and Chakdar et al.
Claim(s) 4, 5, 9, 12, 16, 17, 19, 23, and 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gao et al. in view of Betterle et al. (2020), Front. Plant Sci. 11:237, and Glazer (WO 01/46395 A1, published 06/28/2001).
The instant claims are drawn to a recombinant cyanobacterial host cell described in the above examples, as well as a cyanobacterial host cell comprising a (αβ)3-CpcG heterohexameric phycocyanin disc, wherein the disc comprises three dimers comprising a CpcA and a CpcB linked together by a CpcG, wherein a protein of interest (POI) is fused to the N- or C-terminus of CpcG, and a second POI is fused to the N- or C-terminus of CpcA or CpcB, with an optional cleavage site located between the Cpc protein and the POI.
Betterle et al. teach a CpcB-Xa-IFN fusion protein, where the Xa is a cleavable protein motif and IFN is human interferon α-2 protein. Betterle et al. disclose that this protein creates heterohexamers comprising (CpcB*IFN-CpcA)3-CpcG. Therefore, Betterle et al. teach that CpcB can have an exogenous protein attached to the C-terminus and still assemble into the claimed heterohexamers.
Gao et al. teach YFP attached to the C-terminal end of CpcG, which serves as a linker in the phycobiliosomes that complex into photosystem I and further supercomplex into an NDH-1L-PSI supercomplex. Gao et al. show that CpcG still functions as part of that supercomplex, which still assembles, with the addition of a YFP on the C-terminal (see abstract, Figure S2, whole doc). Therefore, CpcG-YFP will still form (αβ)3-CpcG heterohexameric phycocyanin discs, which are part of the super complex studied in Gao et al. As such, Gao et al. teach a protein of interest (YFP) linked to the C-terminal end of a CpcG, and the production of (αβ)3-CpcG heterohexameric discs comprising CpcA, CpcB, CpcG, and the POI.
Glazer teaches that phycobiliprotein subunits are tolerant to terminal extensions of different sizes, a fusion protein expression system termed "phycobilisome display" (see page 2). Glazer further teaches that this terminal extension, which can be a protein of interest (POI), is “displayed on the surface of oligomer, e.g. the rods of the phycobilisome, and is able to fold into functional proteins while sequestered from interaction with other unfolded polypeptides. Phycobilisome display can therefore be used as an alternative folding environment for difficult-to-fold proteins, especially those that have been found difficult to fold in other organisms.” Glazer teaches that the POI may be separated from the phycobilisome protein by a cleavable linker peptide between the carrier protein and the POI on page 7. Glazer teaches that the POI may be displayed from either the N- or C-terminus of the carrier protein, which is important, as many proteins preferentially tolerate extension on only one of their termini, something that can be advised by the art surrounding the POI (see page 6 for more). Glazer teaches, in the examples, that His tags and biotinylation domains can be attached to the N- and C-terminus of both CpcA and CpcB.
Neither Gao et al., Betterle et al., or Glazer teach a recombinant cyanobacterial host cell comprising two different POIs attached to two different components of a (αβ)3-CpcG heterohexameric phycocyanin discs, as recited in instant claims 5, 9, and 12. However, the concept of using phycobilisomes for presentation of proteins of interest is clearly well established. Glazer thoroughly reviews the concept and recites that the proteins can be cleavable from the complex, a concept executed in Betterle et al., when recombinant IFN is attached to CpcB by a cleavable linker. As Betterle et al. show that proteins can be attached to CpcB without affecting hexamer assembly, Gao et al. show that proteins can be attached to CpcG without affecting complex assembly, and Glazer teaches that protein domains can be attached to CpcA without affecting phycobilisome assembly, it is obvious to one of ordinary skill in the art at proteins can be expressed on the surface of a heterohexameric (αβ)3-CpcG disc as an extension of each subunit. One of ordinary skill in the art would be motivated to combine the teachings of Betterle et al., Gao et al., and Glazer in order to express more than one protein on a heterohexameric (αβ)3-CpcG disc, in order to produce more than one recombinant protein at once. One would be motivated to append multiple proteins to multiple components of the disc so as to be able to recover both proteins from one assembled disc. One would be further motivated to do so as Glazer discloses that presentation on the outside of a heterohexameric disc allows for proper folding of difficult-to-fold proteins or proteins with disulfide bonds (page 2, 8). One would have reasonable expectation of success as the art clearly shows that each of CpcA, CpcB, and CpcG are tolerant to extension of their N- and C-termini and will still assemble into discs. Therefore, instant claims 4, 5, 9, and 12 are obvious over Gao et al., Betterle et al., and Glazer.
Furthermore, both Gao et al. and Betterle et al. teach that this technique can be done in in Synechocystis sp. strain PCC 6803, teaching claim 17, and Glazer teaches that this may be done in Anabaena spp., teaching claim 19. Gao et al. and Betterle et al. teach that the fusion proteins can be expressed under a cpc promotor, teaching instant claim 16. Betterle et al. teach the POI as human interferon α-2 protein, teaching claim 23, and that codon optimization can allow for many eukaryotic proteins to be expressed in a similar manner. Finally, all three sources teach culture of the recombinant organisms, teaching instant claim 24. Therefore, claims 4, 5, 9, 12, 16, 17, 19, 23, and 24 are obvious over the combination of Betterle et al., Gao et al., and Glazer.
Claims 4, 5, 9, 12, 16, 17, 19, 23, 24, and 37 are rejected under 35 U.S.C. 103 as being unpatentable over Gao et al., Betterle et al., and Glazer as applied to claims 4, 5, 9, 12, 16, 17, 19, 23, and 24 above, and further in view of Chakdar et al.
The teachings of Betterle et al., Gao et al., and Glazer regarding claims 4, 5, 9, 12, 16, 17, 19, 23, and 24 are recited above. These sources do not explicitly teach a disc preparation at least 90% pure. However, methods of purification of phycocyanin subunits are known in the art, as reviewed in Chakdar et al., Section 4.4, pages 59-62. Chakdar et al. review several different purification methods and their outcomes. Purification protocol for different cyanobacterial species have different parameters and varying success levels. Chakdar et al. disclose purity ratios of up to 5.59 in this section and in Table 4.1, indicating that high levels of purity can be achieved. One would be motivated to have pure extracts of the discs in order to isolate the proteins produced by the cyanobacteria. It would be obvious to one of ordinary skill in this art to use any method known in the art, such as those presented in Chakdar et al., and optimize said method in order to achieve desired purity. KSR International Co. v. Teleflex Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007), discloses that if a method is “obvious to try”, it is not patentable over the prior art. MPEP § 2144.05(II) recites that routine optimization is “obvious to try”, and therefore supported by said rational. No specific method of purification is used in the specification or recited in the claims to reach this 90% pure preparation. Therefore, any method known in the art can be used to do so. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary, and claim 37 is obvious over Betterle et al., Gao et al., and Glazer in view of Chakdar 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 4, 5, 9, 16, 17, 19, 23, and 24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12,391,950 in view of Vasami et al.
Claim 1 of ‘950 is drawn to a cyanobacterial host cell comprising an expression construct for a fusion protein comprising a POI and a phycocyanin subunit, either CpcA or CpcB, wherein the POI transgene is attached at the 3’ end of the Cpc gene, and thus will be expressed as a C-terminal fusion of the Cpc protein. Further dependent claims specify that the POI is an isoprene synthase (claim 4) or beta-phellandrene synthase (claim 6), as recited in instant claim 23. ‘950 Claims 10-15 recite possible cyanobacterial species, including single celled cyanobacteria, as in instant claim 17, and micro-colonial or filamentous cyanobacteria, as in instant claim 19. Claim 16 recites a culture of the cyanobacterial host cell, as in instant claim 24.
‘950 does not explicitly disclose two proteins of interest linked to both CpcA and CpcB, as in instant claims 4, 5, and 9. However, Vasami et al. teach that two proteins can be expressed from the C-terminal ends of the CpcA and CpcB proteins, and these subunits will still assemble into heterohexameric (αβ)3-CpcG discs (see above for full details on the teachings of Vasami et al.). Therefore, it would be obvious to one of ordinary skill in the art to modify both the CpcA and CpcB proteins by attaching POIs to their C-terminal ends, as in ‘950, and express both at once in a cyanobacterial host cell, such that the proteins will assemble into heterohexameric discs comprising both POIs. One would be motivated to do so in order to produce two POIs, such as an isoprene synthase and a beta-phellandrene synthase, at the same time in the same cell. One would have reasonable expectation of success because Vasami et al. demonstrate that it is possible to express two POIs on the same heterohexameric disc. Therefore, claims 4, 5, 9, 16, 17, 19, 23, and 24 are obvious over ‘950 in view of Vasami et al.
Claims 4, 5, 9, 16, 17, 19, 23, 24, and 37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12,391,950 in view of Vasami et al., further in view of Chakdar et al.
The teachings of ‘950 in view of Vasami et al. regarding claims 4, 5, 9, 16, 17, 19, 23, and 24 are outlined above. These sources do not explicitly teach a disc preparation at least 90% pure. However, methods of purification of phycocyanin subunits are known in the art, as reviewed in Chakdar et al., Section 4.4, pages 59-62. Chakdar et al. review several different purification methods and their outcomes. Purification protocol for different cyanobacterial species have different parameters and varying success levels. Chakdar et al. disclose purity ratios of up to 5.59 in this section and in Table 4.1, indicating that high levels of purity can be achieved. One would be motivated to have pure extracts of the discs taught by ‘950 in view of Vasami et al. in order to isolate the proteins produced by the cyanobacteria. It would be obvious to one of ordinary skill in this art to use any method known in the art, such as those presented in Chakdar et al., and optimize said method in order to achieve desired purity. KSR International Co. v. Teleflex Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007), discloses that if a method is “obvious to try”, it is not patentable over the prior art. MPEP § 2144.05(II) recites that routine optimization is “obvious to try”, and therefore supported by said rational. No specific method of purification is used in the specification or recited in the claims to reach this 90% pure preparation. Therefore, any method known in the art can be used to do so. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary, and claim 37 is obvious over ‘950 in view of Vasami et al., and further in view of Chakdar et al.
Claims 4, 5, 9, 12, 16, 17, 19, 23, and 24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 12,612,638 in view of Vasami et al. and Gao et al.
Claim 1 of ‘638 teaches a cyanobacterial host cell comprising an expression unit encoding a fusion protein comprising a CpcB subunit of phycocyanin and a POI fused to the C-terminus of the CpcB subunit, wherein the POI is an IFN, a tetanus toxin fragment C (TTFC), a Cholera Toxin Fragment B (CtxB), and more. These are proteins recited in instant claim 23. ‘638 claim 2 teaches the expression unit linked to a cpc promotor (as in instant claim 16), ‘638 claims 3-4 disclose a cleavage site between the POI and the CpcB protein, ‘638 claims 6-11 recite species of cyanobacteria that teach the limitations of instant claims 17 and 19, and claim 12 of ‘638 recites a culture of the host cell, as in instant claim 24.
‘638 does not disclose a second POI attached to CpcA or CpcG, as in instant claim 4, 5, 9, and 12. However, Vasami et al. teach that two proteins can be expressed from the C-terminal ends of the CpcA and CpcB proteins, and these subunits will still assemble into heterohexameric (αβ)3-CpcG discs (see above for full details on the teachings of Vasami et al.). Gao et al. teach that proteins can be expressed from the C-terminal end of CpcG and still be incorporated into heterohexameric (αβ)3-CpcG discs (see above for full details on the teachings of Gao et al.). Therefore, it would be obvious to one of ordinary skill in the art to modify more than one of the CpcA, CpcB, and CpcG proteins by attaching POIs to their C-terminal ends, as in ‘638, and express both modified proteins at once in a cyanobacterial host cell, such that the proteins will assemble into heterohexameric discs comprising both POIs. One would be motivated to do so in order to produce two POIs, such as an IFN and a TTFC, at the same time in the same cell. One would have reasonable expectation of success because Vasami et al. demonstrate that it is possible to express two POIs on the same heterohexameric disc. Therefore, instant claims 4, 5, 9, 12, 16, 17, 19, 23, and 24 are obvious over ‘638 in view of Vasami et al. and Gao et al.
Claims 4, 5, 9, 12, 16, 17, 19, 23, 24, and 37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 12,612,638 in view of Vasami et al. and Gao et al., further in view of Chakdar et al.
The teachings of ‘638 in view of Vasami et al. and Gao et al. regarding claims 4, 5, 9, 12, 16, 17, 19, 23, and 24 are outlined above. These sources do not explicitly teach a disc preparation at least 90% pure. However, methods of purification of phycocyanin subunits are known in the art, as reviewed in Chakdar et al., Section 4.4, pages 59-62. Chakdar et al. review several different purification methods and their outcomes. Purification protocol for different cyanobacterial species have different parameters and varying success levels. Chakdar et al. disclose purity ratios of up to 5.59 in this section and in Table 4.1, indicating that high levels of purity can be achieved. One would be motivated to have pure extracts of the discs taught by ‘638 in view of Vasami et al. and Gao et al. in order to isolate the proteins produced by the cyanobacteria. It would be obvious to one of ordinary skill in this art to use any method known in the art, such as those presented in Chakdar et al., and optimize said method in order to achieve desired purity. KSR International Co. v. Teleflex Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007), discloses that if a method is “obvious to try”, it is not patentable over the prior art. MPEP § 2144.05(II) recites that routine optimization is “obvious to try”, and therefore supported by said rational. No specific method of purification is used in the specification or recited in the claims to reach this 90% pure preparation. Therefore, any method known in the art can be used to do so. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary, and claim 37 is obvious over ‘950 in view of Vasami et al. and Gao et al., and further in view of Chakdar et al.
Conclusion
No claim is allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure: Deng et al. (2012) . Deng et al. disclose modification of CpcG by attaching GFP to the N-terminus of CpcG, in Synechococcus under control of a cpc promotor. See section 2.2.
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/AMELIA STEPHENS/Examiner, Art Unit 1645
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
