DETAILED ACTION
Notice of 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 of Group I, claims 1 and 16-20 in the reply filed on 16 January 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The requirement is deemed proper and therefore made Final.
Status of Application
Claims 1-20 are pending; Claims 2-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Thus, claims 1 and 16-20 are subject to examination on the merits.
Priority
The instant application is a 371 of PCT/EP2021/054928 filed 26 February 2021 which claims benefit of foreign priority document EP 20305210.5 filed 28 February 2020 is acknowledged. Said document has been received.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 06 March 2026 and 26 August 2022 have been considered by the examiner. See initialed and signed PTO/SB/08’s.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on p. 26, line 13. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Interpretation
The term “carrier” is interpreted as in the specification to mean a “fusion partner” – See paragraph 0117 of PG-Pub.
Claim Objections
Claim 19 is objected to because of the following informalities: the claim recites several promoters and UTR’s. However, in line three, it appears the “or the” between “psbD promoter and 5′UTR” and “16S rRNA promoter (Prrn) promoter fused with the atpA 5′UTR” is extraneous. Given there are five combinations to choose from, the “or the” between the first and second appears unnecessary.
Appropriate correction is required.
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.
Claim 17 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
The claim recites “wherein said protein, polypeptide or peptide derivative consists in an amino acid sequence at least 80% identical to the amino acid sequence of the recombinant peptide, polypeptide or protein.” It is unclear exactly what is at least 80% to identical to what here because the way the claim is written, the peptide, polypeptide or protein should have 100% identity to itself because nothing in the claim suggests any kind of change or modification has occurred. Second, in order to have any sort of percent identity that can be calculated, you specifically need to know the starting and ending sequences.
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.
Claim(s) 1, 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Mayfield et al. (Curr. Op. Biotech., 2007 – cited on previous PTO-892; hereafter Mayfield NPL) and Mayfield et al. (US 20040014174 – cited on IDS 03/06/2026; hereafter Mayfield PG-Pub) in view of Shoseyov and Stein (US 9783816 – cited on previous PTO-892).
Mayfield NPL teach the following (See Introduction):
Expressing therapeutic proteins in micro-algae has several advantages over other systems employed today. First, chloroplasts have been shown to correctly fold and assemble complex mammalian proteins [2••], and the length of time required from the initial transformation event to having usable (milligram to gram) quantities of a protein can be relatively quick in algae. Stable transgenic lines can be generated in as little at 10 days, and scale-up to production volumes can potentially be achieved a few weeks after this (Figure 1). In addition, algae can easily be grown in full containment reducing any concern about environmental contamination of the therapeutic protein. Moreover, because algae do not have pollen there is no potential for the introduction of transgenes into food crops, as potentially could occur in higher plants by gene flow (via pollen) to surrounding plants [3]. Finally, many green algae fall into the category of Generally Recognized as Safe (GRAS), meaning they are safe to eat, and are therefore potentially a source for the oral delivery of therapeutic proteins, perhaps with little or no purification. The potential of eukaryotic algae as a production platform for recombinant proteins with therapeutic and other uses will be discussed.
It is further taught that stable transformation of the chloroplast Chlamydomonas reinhardtii, which is a species within the Division of Chlorophyta (pertaining to claim 20), has been established for efficient expression of important proteins with the added benefit of inexpensive hosts and high yields (See Figure 2 and Conclusion). Increases in expression of foreign proteins in the chloroplast requires codon optimization (See p. 128, “Increase expression though codon optimization” – entire section); and the selection of appropriate promoters, wherein the most efficient promoters are atpA or pbsD and 5’ UTR’s (See p. 128, 2nd col., “Promoters and UTRs for increased protein expression”).
Mayfield PG-Pub teach methods of producing one or more polypeptides in a micro-algae chloroplast, including methods of producing polypeptides and fusion polypeptides, including tags for easy isolation of proteins such as His-tags, Flag tags, etc. (See paragraph 0102), that specifically associate in a plant chloroplast to generate a functional protein complex. To this end, they teach the exact vectors, methods, codon optimization strategies, promoters, etc. for production of proteins of interest in the chloroplast of the micro-algae C. reinhardtii (See claims 1-207 and Examples; paragraphs 0075-0077, 0106). Specific promoters utilized in the Examples are atpA and rbcl promoters and rbcl 3’ UTR (See paragraph 0146); atpA or rbcl 5’ UTR (See paragraphs 0066, 0307).
Mayfield NPL and Mayfield PG-Pub, however, do not teach wherein it is the chloroplasts of a microalgae that is transformed to produce said collagen.
Shoseyov and Stein teach producing collagen that is codon optimized for expression in plants by expressing nucleic acids encoding said collagen and exogenous PH4 (prolyl-4-hydroxylase) in said plant genome in order to produce high levels of hydroxylated collagen chains capable of forming native triple helix type I collagen fibers (See Abstract, Col. 1, lines 28-33; Example 1). It is stated, that while collagen has been attempted to be expressed in various plants previously, high levels have not been achieved due to insufficient hydroxylation. They further teach for successful hydroxylation and therefore collagen production to occur, said collagen and hydroxylating enzyme (e.g. PH4) need to be sequestered in the plant (See Col. 2, lines 31 to Col. 3, line 3). It is further taught that said genome can be the chloroplast genome and that said techniques are known in the art and explained therein – See Col. 15, lines 35-62).
Therefore it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to utilize the microalgae Chlamydomonas reinhardtii and to transform the chloroplast of this algae with codon optimized collagen and PH4 under the control of atpA or pbsD and 5’ UTR’s as taught by both Mayfield’s in order to produce the collagen of Shoseyov and Stein because Mayfield NPL and Mayfield PG-Pub teach the advantages of using host microalgae to produce recombinant proteins of interest and specifically the production of heterologous proteins in the chloroplasts. In addition, Mayfield NPL and Mayfield PG-Pub teach that utilizing microalgae like Chlamydomonas reinhardtii offer the potential to produce high yields of recombinant proteins more rapidly and at much lower cost compared to other kinds of recombinant protein production; as well as the advantage over recombinant production of proteins in plants because said algae do not contain pollen and therefore there is no potential for introduction of transgenes to other neighboring crops (See Mayfield NPL, Introduction). These would be motivation in and of itself for a skilled artisan. There would be a reasonable expectation of success in producing the collagen of Shoseyov and Stein utilizing the chloroplasts of Chlamydomonas reinhardtii of Mayfield NPL and Mayfield PG-Pub, rather than the plant chloroplasts of Shoseyov and Stein in the method of expressing collagen and PH4 in chloroplasts because both Mayfield’s teach of the many successes of other skilled artisans (See Table 1 of Mayfield NPL), Mayfield PG-Pub teaches the exact methods, vectors, promoters, codon optimization strategies for successful production of proteins in chloroplasts of Chlamydomonas reinhardtii (See Examples); and finally, also because the chloroplast offers a place to sequester both the PH4 and collagen for correct hydroxylation and therefor collagen production.
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, 16-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16-37 of copending Application No. 17800063 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the combination of claims of the ‘063 application render obvious the instant claims.
The instant claims in their broadest are drawn to a recombinant microalgae comprising a nucleic acid sequence encoding a recombinant protein, polypeptide or peptide comprising repeat units of amino acids, said protein, polypeptide or peptide being chosen from collagen, elastin and their derivatives, and said nucleic acid sequence being located in the chloroplast genome of microalgae (claim 1). Dependent claims recite 18 recites the protein, polypeptide, or peptide is fused to a carrier (interpreted as a fusion partner, as noted above – claim 18), and wherein said microalgae is chosen from the group consisting of Chlorophyta, Chlorophyceae, Pleurastrophyceae, Prasinophyceae, Chromophyta, Bacillariophyceae (diatoms), Chrysophyceae, Phaeophyceae, Eustigmatophyceae, Haptophyceae, Raphidophyceae, Xanthophyceae, Cryptophyta, Cryptophyceae, Rhodophyta, Porphyridiophycea, Stramenopiles, Glaucophyta, Glaucocystophyceae, Chlorarachniophyceae, Haptophyceae, Dinophyceae, Scenedesmaceae, Euglenophyta, Euglenophyceae (Claim 20).
The claims to the ‘063 application in their broadest are drawn to recombinant algae comprising a recombinant protein, polypeptide, or peptide of interest fused to aprotinin and methods of making said fusion proteins (Claims 16, 19, 20), wherein the protein of interest is selected from ollagen, collagen like and matricins proteins, polypeptides or peptides, wherein the matricins are chosen from elastin and elastin like proteins (claims 21-23) and wherein algae is chosen from the group consisting of Chlorophyta, Chlorophyceae, Pleurastrophyceae, Prasinophyceae, Chromophyta, Bacillariophyceae, Chrysophyceae, Phaeophyceae, Eustigmatophyceae, Haptophyceae, Raphidophyceae, Xanthophyceae, Cryptophyta, Cryptophyceae, Rhodophyta, Porphyridiophycea, Stramenopiles, Glaucophyta, Glaucocystophyceae, Chlorarachniophyceae, Haptophyceae, Dinophyceae, Scenedesmaceae, Euglenophyta, Euglenophyceae and Cyanophyceae (Claim 24), and wherein the fusion proteins are produced in chloroplasts of the algae (Claim 37).
In construing the scope of the claims of the ‘063 application, the term “algae” or to mean “microalgae”, which is defined as having a chloroplast (paragraph 0052) and that the recombinant protein is produced in said chloroplast (paragraph 0055) – See Construing Scope of the Claims, MPEP 804(II)(B)(1)). As such, the combination of claims in the ‘063 application necessarily arrives at fusion protein of aprotinin fused to collagen or elastin like proteins, polypeptides or peptides, and produced in the chloroplasts of microalgae, which necessarily renders obvious the claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUZANNE M NOAKES whose telephone number is (571)272-2924. The examiner can normally be reached M-F (7-4).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached at 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656 17 March 2026