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 .
Status of Claims
The preliminary amendment filed on 1/25/2024 cancelled claims 1-43 and added new claim 44-57. There are no claims withdrawn and no claims amended. Claims 44-57 are pending and will be examined on the merits.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/129,877, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. '877 fails to disclose, either in the specification, claims, or drawings, a '5HVZ domain' or 'an smAKAP domain', nor the linking of those domains to VHH antibodies, nor a recombinant Spirulina comprising those domains. Therefore, the provisional application of ‘877 does not relate to the instant claims of the application. Thus, for the purposes of applying prior art, claims 44-57 have the effective filing date of 12/23/2021, the date PCT/US21/65138 was filed. No claims have the effective filing date of 12/23/2020, the date that provisional application 63/129,877 was filed. Should applicant disagree with the examiner’s factual determination above, applicant may point to the particular places in provisional application 63/129,877, for example, page and line numbers or figures, which disclose support for instant claims 44-57.
Information Disclosure Statement
The Information Disclosure Statements filed on 01/25/2024, 05/10/2024, and 10/08/2024 have been considered. Signed copies are enclosed.
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.
Claims 44-51 and 57 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 term “5HVZ domain” in claims 44-48 is an undefined term which renders the claim indefinite. The term “5HVZ domain” is not defined by the claim, the specification does not provide a definition for 5HVZ, and 5HVZ does not have a commonly known definition in the art of Spirulina biology or recombinant protein expression, so one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The specification offers the definition of "a 5HVZ can be a smAKAP AKB domain bound RIa dimerization/docking (D/D) complex” (paragraph [0081]); however, this is not definitive, and contradicts the claim, where 5HVZ is defined as a domain, not a complex. The specification offers further context in paragraph [0203]: “The presence of a 5HVZ dimerization motif in a polypeptide acts as a docking platform which mediates protein-protein interactions between three α-helical chains, placing the monomers antiparallel to one another.” This passage gives the idea that the 5HVZ domain is a dimerization motif; however, the specification still does not provide an amino acid sequence for the domain, nor any formal definition.
The specification does point to Burgers et al. (2016) FEBS J. 283(11):2132-2148; however, Burgers et al. still does not provide a definition for “a 5HVZ domain”; the only 5HVZ mentioned in Burgers et al. is the Protein Data Bank accession number 5HVZ for the structural data from the study. When one is able to find the PDB deposit, there are at least three sequences, none of which are defined as a “5HVZ domain”, and multiple versions of the entry; which version corresponds with the instant specification is not defined. Moreover, the PDB deposit and the Burgers et al. paper, taken together, define the 5HVZ accession number as a rendering of the crystal structure of a non-covalently bound complex between smAKAP’s A-kinase binding domain (smAKAP-AKB) and the type I regulatory subunits (RI) of cAMP-dependent kinase (PKA) (PKA-RI) (abstract). Again, a complex between two non-covalently bound different proteins, by definition, cannot be a domain in a protein; a domain is defined as “distinct functional and/or structural unit in a protein” (European Bioinformatics Institute). As the two complexed proteins are different from each other, it is unclear which protein contains the “5HVZ domain”, and thus one of ordinary skill in the art would not even be able to deduce which protein the domain might be derived from.
Therefore, the term “5HVZ domain” is meaningless, taken in view of the specification, the provided references, and the art as a whole. Applicant would need to structurally define “a 5HVZ domain” for one of ordinary skill in the art to be able to interpret the instant claims. Claims 49-51 and 57 inherit this rejection, as they are dependent on claim 44 and/or 47.
For the purposes of examination, the term “5HVZ domain” will be interpreted as any functional linking domain connected to a VHH antibody.
Claim 51 recites the limitation "the smAKAP peptide" in line 1 and “the WT smAKAP peptide” in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 51 is dependent on claim 44, which recites “an smAKAP domain”. It is unclear if the peptide of claim 51 only comprises the domain of claim 44, or if it contains additional domains, or only part of the domain. Moreover, the “WT smAKAP peptide” of claim 51 has no antecedent basis in claim 44. Correction is required.
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.
Claims 52, 55, and 56 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jester et al., bioRxiv, 25 pages (January 27, 2021), as evidenced by Burgers et al., FEBS J. 283(11):2132-2148 (2016) and RCSB Protein Data Bank accession number 5HVZ, accessed 1/29/2026.
Instant claim 52 is drawn to an engineered polypeptide, comprising from N- to C-terminus, a first VHH antibody sequence; an smAKAP domain; and a second VHH antibody sequence. Claim 55 is drawn to a recombinant Spirulina expressing the engineered polypeptide of claim 52, and claim 56 is drawn to a nucleic acid comprising a sequence encoding for the engineered polypeptide of claim 52. Pages 54-55 of the instant specification define the sequence of an smAKAP domain as SEQ ID NO: 389.
Jester et al. describe the expression of antigen-binding domains (VHHs) derived from camelid single-chain antibodies in Spirulina. Jester et al. further discloses “VHHs…constitutively expressed in Spirulina from the strong promoter Pcpc600 in various formats, including…dimers…” on page 6. In Figure 3, the dimer is clearly depicted in the format VHH – scaffold protein (labeled 5HVZ) – VHH. This dimeric scaffolding protein is identified as 5HVZ in the Figure 3 legend. 5HVZ is not defined in Jester et al., but the citation for the dimer refers to Burgers et al., also cited in the instant specification. The Burgers et al. paper provides the definition for 5HVZ as a deposit code for the ECSB Protein Data Bank (PDB). The entry for 5HVZ on the PDB discloses the sequence identical to SEQ ID NO: 389. Therefore, the dimer presented in Jester et al. is an engineered polypeptide comprising from N- to C-terminus, a first VHH sequence, an smAKAP sequence, and a second VHH sequence, meeting the limitations of instant claim 52. Moreover, the expression of the dimer of Jester et al. in Spirulina meets the limitations of instant claim 55. Finally, as ‘constitutive expression’ and ‘promotors’ are known in the art to refer to transcription of a nucleic acid, the Spirulina containing the dimer of Jester et al. would contain a nucleic acid comprising a sequence encoding for the dimer, meeting the limitations of instant claim 56.
Therefore, instant claims 52, 55, and 56 are anticipated by Jester et al., as evidenced by Burgers et al. and PDB accession number 5HVZ.
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 52-56 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7-11, 13, 16, and 18 of copending Application No. 19/422,077 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they are ultimately drawn to the same protein and/or organism.
Claims 52-56 are drawn to an engineered polypeptide, comprising, from N- to C-terminus, a first VHH antibody sequence; an smAKAP domain; and a second VHH antibody sequence. Claims 53 and 54 further limit the polypeptide of claim 52, defining possible sequences for the smAKAP domain. Claim 55 is drawn to a recombinant Spirulina expressing the polypeptide of claim 52, and claim 56 is drawn to a nucleic acid comprising a sequence encoding the polypeptide of claim 52.
The claims of ‘077 are primarily drawn to a recombinant smAKAP peptide, comprising an amino acid sequence of SEQ ID NO: 2 with at least one amino acid substitution selected from a list. SEQ ID NO:2 with the amino acid substitutions C16S and C24S leads to the instant SEQ ID NO: 390, as claimed in instant claim 54, and less either of these mutations meets the limitations of instant claim 53. Instant claims 53 and 54 are dependent on claim 52, which requires VHH antibody sequences on each end of the smAKAP sequence; ‘077 claim 13 recites “The recombinant smAKAP peptide of claim 1, wherein the recombinant smAKAP peptide is linked to two VHH antibodies, wherein a first VHH is at a C-terminus and a second VHH is at an N-terminus of the recombinant smAKAP peptide.” Therefore, ‘077 claim 13 meets the limitations of instant claims 52-54. Additionally, ‘077 claims 7-11 are drawn to various additions of ‘heterologous moieties’ to the peptide of ‘077 claim 1, and define this heterologous moiety as possibly a VHH antibody, which also meets the limitations of instant claim 52. Instant claim 55 is drawn to a recombinant Spirulina expressing this peptide, and ‘077 claim 16 is drawn to a recombinant Spirulina comprising the recombinant smAKAP peptide of ‘ claim 1. As claim 1 uses the language ‘comprising’, the addition of the VHHs required by claim 52 and 55 can be included in the recombinant Spirulina of ‘077 claim 16. Similarly, instant claim 56 is drawn to a nucleic acid comprising the sequence of the peptide of claim 52, and ‘077 claim 18 is drawn to a vector encoding the recombinant smAKAP peptide of claim 1. A vector is understood in the art to be a nucleic acid, and therefore, ‘077 claim 18 meets the limitations of instant claim 56.
Therefore, claims 1, 7-11, 13, 16, and 18 of ‘077 anticipate instant claims 52-56.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed. 18. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Amelia C 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
/DANIEL E KOLKER/Supervisory Patent Examiner, Art Unit 1645