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 amendment filed on 05/21/2026 amended claims 44, 46-51, and 57, added new claim 58, and cancelled claim 45. Claims 1-43 were previously cancelled. Claims 44 and 46-58 are pending and will be examined on the merits.
Information Disclosure Statement
The Information Disclosure Statement filed on 05/21/2026 has been considered. Signed copies are enclosed.
Response to Amendment
The amendment filed 05/21/2026 in response to the office action mailed 02/05/2026 is acknowledged. The rejections set forth under 35 USC § 102 are withdrawn for the following reasons:
The Declaration under 37 CFR 1.132 filed 05/21/2026 is sufficient to overcome the rejection of claims 52, 55, and 56 based upon 35 USC § 102.
Maintained or modified rejections are set forth below, as necessitated by the amendments. Responses to arguments follow.
Maintained Claim Rejections - 35 USC § 112 - Modified as Necessitated by Amendment
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, 46-51 and 57-58 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, and 46-48 is an undefined term which renders the claim indefinite. The term “5HVZ domain” is not sufficiently 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. Claim 44 recites “a 5HVZ domain as described in Protein data Bank (PDF) entry 5HVZ version 1.3”. 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, similar to claim 44. 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, although the claim defines the version as 1.3. The differences between versions, however, 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. The PDB entry does provide the sequences for three chains; however, this is insufficient, as which none of the chains are explicitly labeled as “5HVZ domain”.
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 57-58 inherit this rejection, as they are dependent on claim 44 and/or 47.
Response to Arguments
Applicant's arguments filed 05/21/2026 have been fully considered but they are not persuasive. Applicant argues that the 5HVZ domain is defined in terms of Burgers et al. (2016) in paragraph [0203] of the specification, and that the sequence of the domain can be found online, available at https://www.rcsb.org/versions/5HVZ. Applicant argues that a person of ordinary skill in the art can identify the domain from this entry, as chains A and B are identical, representing a homodimer, and chain c is clearly labeled as “Small membrane A-kinase anchor protein”, corresponding to the smAKAP sequence of the disclosure. Applicant is willing to directly incorporate the appropriate sequence into the specification, upon the Office's request.
Examiner acknowledges confirmation that the 5HVZ domain is listed in the PDB entry. However, the definition of a term integral to the claim must be clearly articulated in the written description, as per MPEP §2173.05(a). “The meaning of every term used in a claim should be apparent from the prior art or from the specification and drawings at the time the application is filed.” As currently recited in the claims, the 5HVZ domain’s sequence, which is integral to the present invention, is not provided in the specification or the drawings, nor is 5HVZ a term widely known in the art. The specification, and instant claim 44, merely direct the reader to the sequence, which is hosted externally at the link provided. The external location of the sequence of the 5HVZ domain provides the potential for indefiniteness; if the external source were to change, disappear, or so on, one would not be able to ascertain the sequence of the 5HVZ domain. Examiner therefore requests that the 5HVZ sequence be submitted with a SEQ ID NO and added to the instant specification. This will not constitute new matter, as the sequence is disclosed by the Burgers et al. source and the PDB entry that is incorporated by reference. Examiner suggests amending claim 44 to recite the SEQ ID NO that corresponds to the 5HVZ domain, which would provide appropriate clarity for the instant claims.
New Claim Rejections - 35 USC § 112
Claim 50 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 50 recites the limitation "the recombinant " in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 50 depends from claim 44, which no longer recites “a recombinant Spirulina”. Examiner suggests amending claim 50 to recite “wherein the complex comprises a maltose binding protein (MBP)” in order to overcome this rejection.
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.
Response to Arguments
Applicant's arguments filed 05/21/2026 have been fully considered but they are not persuasive. Applicant is willing to file a Terminal Disclaimer, but has asked the rejection to be held in abeyance until allowable subject matter is identified. The rejection is therefore upheld.
Closest Prior Art
Claims 44 and 46-58 are free of the prior art as of the effective filing date of 12/23/2021. The closest prior art is:
Alvarez-Cienfuegos et al. (2016) Sci Rep 6, 28643: discloses the concept of attaching VHH antibodies to a domain that forms a trimer, in order to create monospecific “trimerbodies”.
Burgers et al. (2016) FEBS J. 283(11):2132-2148: discloses the binding complex of a 5HVZ dimer and an smAKAP peptide.
There is no motivation in the prior art to use the 5HVZ domain and a smAKAP peptide to create multimeric VHH antibodies, similar to those of Alvarez-Cienfuegos. Therefore, the inventive concept of the instant claims is free of the art as of the effective filing date of 12/23/21.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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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