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 06/04/2026 is acknowledged.
Claims 11-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/04/2026.
Status of Claims
Claims 1-20 are pending. Claims 11-16 are withdrawn. Claims 1-10 and 17-20 will be examined on the merits.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The Information Disclosure Statement filed on 12/21/2023 has been considered. Signed copies are enclosed.
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.
Claim Rejections - 35 USC § 112
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 1-9 and 17-20 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 claim(s) 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 inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
Claims 1-9 are drawn to any recombinant algae comprising synthetic nucleotide sequences for spider silk protein, tRNAs, and SHMT. Claim 17 is drawn to a method of producing said algae, and claims 18-20 are drawn to a method of producing spider silk with the algae of claim 1. The specification teaches, on page 9, that algae is defined as “any photosynthetic microscopic organism”. The specification teaches one example of such a recombinant algae, in the species Cyanobacteria aponinum. This algae meets the written description provision of 35 USC 112(a). However, the claims encompass far more than C. aponinum, and are drawn to any algae, or, as defined by the instant specification, any photosynthetic microorganism.
The state of the art of protein production using algae is still emerging. Indeed, while families such as Chlamydomonas and Chlorella are commonly used to produce proteins, as reviewed in Banerjee et al. (Current Opinion in Biotechnology, (2022) 78:102784) (see Table 1). As stated by Banerjee et al., most protein expression in microalgae is done in C. reinhardtii, and many problems with protein titers, construct stability, and transformability have impeded mass commercialization. Additionally, as stated in Jiji et al. (Vegetos, (2024), 37(3), 788-793), stable transformants are not common among algae species, and only a few microalgae are commercially viable at this time (see Table 1 and section “Challenges in making algal vaccines” on page 4). Therefore, the state of the art does not support the concept of any conceivable algae being used as a recombinant algae for protein production. Therefore, the full extent of claim 1 does not have sufficient written description support in light of the specification and the state of the art.
Moreover, claims 7, 8, and 17 are drawn to sequences from the genome of C. aponinum as specific insert sites for the constructs of the instant specification. This is not supported by the breadth of the claims. While C. aponinum may have the sequences (which is not guaranteed, as strain to strain variation can occur), not all algae will have these sequences at which to insert the constructs of the current invention. Therefore, claims 7, 8, and 17 do not have sufficient written description support for the breadth of the claims. Additionally, claim 1 recites SEQ ID NOs: 9-11 as encoding the tRNAs and SHMT. The instant specification discloses on page 23 that these are from the genome of C. aponinum. It is known in the art that species have optimized tRNAs for protein expression in that cell (see Tran et al., (Genome biology and evolution, (2016), 8(1), 282-295) and Kanaya et al. (Gene, (1999) 238(1), 143-155)). Therefore, while the tRNAs of claim 1 may work to enhance protein expression in C. aponinum, there is no indication that these tRNAs would function just the same in any algae species. Therefore, the explicit recitation of SEQ ID NOs in claim 1 is incongruent with the breadth of the preamble, which recites any algae.
Overall, based on the disclosure, the state of the art at the time of filing, a skilled artesian would have recognized that the applicant was not in possession of the breadth of the claimed invention at the time of filing. Consequently, in accordance with the MPEP, only the disclosed example of C. aponinum has full written description support in terms of the functionality of the SEQ ID NOs disclosed in the claims. In view of the art, only the strains of algae commonly used in the art of protein expression, such as those recited in claim 10, meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
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.
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) 1, 2, 9, 10, and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Molino et al. (2016), Research Ideas and Outcomes 2:e9342 in view of WO 2014052975 A1, Clark et al., published 4/3/14.
Molino et al. teach a recombinant strain of Chlamydomonas reinhardtii expressing recombinant spider silk protein MaSp1. Molino et al. teach the spider silk protein integrated into the chromosome of C. reinhardtii (see page 6 and Figure 3). Molino et al. disclose cultivating the strain in TAP at temperatures of 20-25°C (see page 8, Figure 4) to produce the protein of interest.
Molino et al. do not disclose the recombinant algae as containing tRNA or SHMT sequences. Molino et al. also do not disclose culturing in BG11 or UPA medium or with .01-5% carbon dioxide.
Clark et al. disclose expression systems for up-regulating protein production in claim 1, paragraphs [0096] and [00100], comprising a host cell and synthetic spider silk polypeptide, synthetic tRNA, and SHMT encoding nucleotide sequences. Clark et al. disclose there may be 2, 3, 4, or 8 copies of the spider silk protein MaSP1 (see paragraph [0097] and [00114]). Clark et al. disclose increased efficiency of the system from increasing the tRNA pools for glycine and conversion of serine to glycine via SHMT (Example 7-8 and paragraph [00110]). The tRNAs used in the example of Clark et al. originate from the host cell, E. coli (see paragraph [00160]). The conditions used to produce the protein are disclosed in paragraph [00168]), and comprise bioreactor media at 37°C.
Neither Clark et al. nor Molino et al. explicitly disclose a recombinant algae comprising at least one motif of spider silk protein, at least two tRNA sequences, and at least one SHMT sequence, as claimed in instant claim 1. However, this invention is obvious in view of the combination of Clark et al. and Molino et al. Molino et al. teach the expression of spider silk proteins via integration of a multimeric cassette into the genome of C. reinhardtii, a commonly used algae for protein production. Clark et al. teach that including the endogenous tRNA and SHMT nucleotide sequences results in 20-fold better production of a spider silk protein, due to the large number of glycines present in an MaSp1 motif (see Example 8, paragraph [00110] and [00176], and Figure 25). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date to express the spider silk motif in an algae and to additionally express the glycine tRNAs and SHMT as well, in order to increase production of spider silk. One would be motivated to do so, as algae like C. reinhardtii have GC rich genomes, similar to the spider silk motif, which allows for increased heterologous expression (see Molino et al., page 6, second paragraph). One would have a reasonable expectation of success when using the tRNA and SHMT of the host organism as this allows for better expression and codon recognition (see paragraph [00152] of Clark et al.). Taken together, the invention of claims 1, 2, 9, 10, and 18 is obvious over Molino et al. in view of Clark et al.
Claim(s) 1-6, 9, 10, and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Molino et al. in view of Clark et al. as applied to claims 1, 2, 9, 10, and 18 above, and further in view of Foo et al., (2006) Applied physics A, 82(2), 193-203.
The teachings of Molino et al. in view of Clark et al. regarding claims 1, 2, 9, 10, and 18 are discussed above. Neither Molino et al. nor Clark et al. explicitly disclose the motif of SEQ ID NO: 1 or 2, although both contain very similar sequences for MaSp1 protein motifs. Neither Molino et al. nor Clark et al. explicitly disclose 10, 18, 36, or 20 copies of the motif as in instant claims 3-6 and SEQ ID NO: 12-15.
Foo et al. discloses a consensus sequence for MaSp1 spider silk as “SGRGGLGGQGAGAAAAAGGAGQGGYGGLGSQG” in Table 1, which is the amino acid sequence of SEQ ID NO: 1. See alignment below. Foo et al. also disclose multiples copies of this sequence (16).
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While the nucleic acid sequences of SEQ ID NO: 12-15 are not disclosed by the art, it would be obvious to one of ordinary skill in the art to optimize the nucleic acid sequence Foo et al. into that of SEQ ID NO:1 in order to optimize codon usage in the host organism. As recited by Clark et al., paragraph [0110], modifying the nucleic acids encoding the spider silk sequences so that codon usage corresponds to the tRNA pool available in the host organism results in more effective expression systems for the production of repetitive recombinant spider silk proteins. Regarding the number of repeats of the spider silk motif of Foo et al., the instant specification does not provide any reasoning or justification for the selection of 10, 20, 18, or 36 copies of the spider silk motif. The instant specification does not show any unexpected results that indicate a special advantage of 10, 20, 18, or 36 copies of the spider silk motif. Clark et al. disclose 2-8 copies of the spider silk motif in paragraphs [0097] and [00114]. Clark et al. further disclose up to 14 total repeats of a spider silk motif in paragraph [00163], in order to result in a larger repetitive spider silk protein. Therefore, as spider silk is known to come in repeated motifs such as that of SEQ ID NO:1, as disclosed in Foo et al. and Clark et al., and additional repeats will result in larger proteins, one of ordinary skill in the art would be motivated to pick any multiple of sequences and express the motif in that quantity in order to obtain proteins of different sizes. One would have a reasonable expectation of success, as Clark et al. demonstrate a 20 fold increase in protein production when using 14 copies of a spider silk motif expressed in the presence of additional tRNAs (see Clark et al. Example 8, paragraph [00110] and [00176], and Figures 25-29). Therefore, claims 1-6, 9, 10, and 18 are obvious over Molino et al., Clark et al. and Foo et al.
Claims 1, 2, 9, 10, and 18-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Molino et al. in view of Clark et al. as applied to claims 1, 2, 9, 10, and 18 above, and further in view of Gris et al., (2017) Journal of Applied Phycology, 29(4), 1781-1790.
The teachings of Molino et al. in view of Clark et al. regarding claims 1, 2, 9, 10, and 18 are discussed above. Neither Molino et al. nor Clark et al. explicitly disclose the conditions for culturing the algae as BG11 medium, UPA medium, or with air fortified with carbon dioxide from .01%-5%. However, it is well known in the art that optimal growing conditions vary for species to species. For algae like Cyanobacteria, optimal conditions include 5% CO2, 30-40°C, and BG11 medium, as taught in Gris et al., to maximize protein production. Therefore, claims 18-20 are not novel and are obvious in view of the art.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Amelia Stephens whose telephone number is (571)272-1006. The examiner can normally be reached M-F 8-5 EST.
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/AMELIA STEPHENS/Examiner, Art Unit 1645
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
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