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 .
MATTER OF RECORD
Election by Original Presentation
Newly amended claim 10 and claim 13 are now directed to an invention that is independent or distinct from the invention originally claimed for the following reasons:
Claim 10 is amended to recite an isolated polynucleotide sequence encoding the fusion polypeptide of claim 1. Claim 13 is amended to recite a method of analyzing the structure of a target protein comprising crystalizing the target protein with a fusion polypeptide according to claim 1.
Applicant has received an action on the merits for the originally presented invention; a fusion polypeptide comprising a first polypeptide which is an antigen-binding domain and a second polypeptide which is a polypeptide scaffold, wherein the antigen binding domain is linked by a peptide linker at its C-terminus to the N-terminus of the polypeptide-scaffold and wherein said peptide linker consists of one or more proline residues and a complex comprising said polypeptide and a target protein.
Therefore, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 10 and 13 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Status of Application, Amendments and/or Claims
The amendment and Applicant's arguments, filed 09 January 2026 and 05 March 2026, have been entered.
Claims 5, 7, 8, 14 and 15 are canceled. Claims 10 and 13 are withdrawn from consideration as being drawn to a non-elected invention. Claims 1, 3, 9 and 11 are amended. New claims 16-21 are added. Claims 1-4, 6, 9, 11, 12, 16-21 are under examination.
Withdrawn Objections And/Or Rejections
The objection to the specification because of sequence deficiencies, as set forth
at pages 3-6 of the previous Office Action (10 September 2025), is withdrawn in view of the amendment (09 January 2026 and 05 March 2026).
The objection to claim 13, as set forth at page 6 of the previous Office Action (10 September 2025), is withdrawn in view of the amendment (09 January 2026).
The rejection to claims 3, 5, 13-15 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as set forth at page 7 of the previous Office Action (10 September 2025), is withdrawn in view of the amendment (09 January 2026).
The rejection to claims 1-4, 6-10, 12-15 under 35 U.S.C. 102(1) as being anticipated by Brunner et al. (Structural basis for ion selectivity in TMEM175K+channels. "bioRxiv; posted 04 December 2018), as set forth at pages 16-17 of the previous Office Action (10 September 2025), is withdrawn in view of Applicant’s arguments that the proline depicted in the figure of Brunner et al. belongs to the nanobody (Nb) not the linker (09 January 2026).
The rejection to claims 1 and 5 are under 35 U.S.C. 103 as being unpatentable over Brunner et al. (Structural basis for ion selectivity in TMEM175K+channels "bioRxiv; posted 04 December 2018) in view of Beauprez et al. (US 2022/0259631; published 18 August 2022, priority date 19 July 2019) and Morcos et al. (Coevolutionary signals across protein lineages help capture multiple protein conformations. PNAS Vol. 110/No. 51, pages 20533-20538; December 17, 2013), as set forth at pages 17-22 of the previous Office Action (10 September 2025), is withdrawn in view of Applicant’s arguments that the proline depicted in the figure of Brunner et al. belongs to the nanobody (Nb) not the linker (09 January 2026)..
Specification
The disclosure remains objected to because it contains an embedded hyperlink and/or other form of browser-executable code (please see pages 6 and 27). 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.
The basis for this rejection is set forth at page 6 of the previous Office Action (10 September 2025).
The Examiner notes that deleting “http://” would obviate this objection.
The scientific reasoning and evidence as a whole indicates that the objection should be maintained.
Claim Rejections-35 USC § 112(a) or 35 U.S.C. 112 (pre-AIA ), First paragraph, Written description
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 1-4, 6, 9, 12 (and new claims 16-21) remain 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.
The basis for this rejection is set forth at pages 7-15 of the previous Office Action (10 September 2025).
APPLICANT’S ARGUMENTS: Applicant argues that without acquiescing to the rejection and solely in the interest of expediting prosecution, claim 1 is amended to more precisely define both the antigen-binding domain and the polypeptide scaffold of the claimed fusion polypeptide. Applicant submits that the specification as originally filed demonstrates that Applicant had possession of the claimed subject matter in accordance with the written description requirement of 35 U.S.C. §112(a) at the time of filing.
Applicant’s arguments have been fully considered but are found persuasive for the following reasons:
1. As was stated in the previous Office Action, the instant claims require the use of undisclosed VHH antigen binding domains. The instant claims recite a function; the function of binding to an antigen, but fail to recite a structure (i.e., a particular SEQ ID NO: for the VHH antigen binding domain). Accordingly, the claims recite a vast genus of fusion polypeptides that comprises a VHH domain with a functional limitation, but no structural limitations.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through establishment of a structure-function correlation (show a structure is correlated with the function) OR through a sufficient description of a representative number of species (show a representative number of species that have the function. There must be enough species that are representative of the full breadth of the genus).
2. References were cited in the previous Office Action, which teach nanobodies (Nbs). The references teach the binding affinities and specificities of the variable domains of the heavy chain of camelid heavy-chain antibodies (VHHs) to their cognate antigens are similar to those of conventional Abs.
The references teach that nanobodies (Nbs) are single domain antibodies (sdAbs) based on the variable domain of natural heavy chain-only Abs (HCAbs) found in camelids (e.g. dromedaries, llamas) and are also referred to as VHHs (for VH of HCAbs). The art teaches that despite being composed of a single VHH domain of small molecular size, Nbs bind their cognate antigens with affinities and specificities similar to those of conventional Abs with heavy (H) and light (L) chains. Their small size and long
CDRs allow them to recognize epitopes located in clefts and protein cavities (e.g. the
active sites of enzymes, conserved inner regions of surface proteins from pathogens),
which are frequently less accessible to conventional Abs.
The binding specificity/affinity of a VHH to its cognate antigen is determined by the sequence/structure of the VHH. The skilled artisan cannot extrapolate from the instant specification, established possession of the breadth of the VHH domains encompassed by the instant claims. There is no information regarding what structural features would likely be associated with such binding activity. Those of ordinary skill in the art could not predict which amino acids can vary within the VHH without losing binding activity, particularly in view of the molecular chaperone intentions of the fusion polypeptides. The number of structures encompassed by the claims may be vast or conversely there may be no structures that possess the claimed function. The combination of cited evidentiary publications underscores a lack of structure-function correlation in VHH.
3. New claims 19-21 recite SEQ ID NO:9, SEQ ID NO:11 and SEQ ID NO:12, respectively. The claims recite a structure (SEQ ID NOs) but these claims lack written description.
SEQ ID NO:9 comprises the amino acid sequence of a polypeptide-scaffold. SEQ ID NO:11 comprises the amino acid sequence of a di proline linker and a maltose binding protein (MBP). SEQ ID NO:12 comprises the amino acid sequence of VLV, a di proline linker and a maltose binding protein (MBP). None of the amino acid sequences recite the structure of a defined VHH antigen-binding domain.
4. The written description requirement for a claimed genus may be satisfied through a sufficient description of a representative number of species (show a representative number of species that have the function).
However, the instant specification fails to describe a representative number of species to provide adequate written description of the claimed genus as per MPEP § 2163.
The specification teaches 2 fusion polypeptides with a defined VHH antigen-binding domain structure (SEQ ID NO: 1 and SEQ ID NO: 2).
Two fusion polypeptides with a defined VHH antigen-binding domain structure is not representative of an entire genus of fusion polypeptides wherein the VHH antigen-binding domain comprises an unlimited number of different structures. The disclosed species is not representative of the genus because the genus is highly variant and encompasses an unlimited number of individual and combination substitutions.
There is no evidence that the disclosed fusion polypeptides are representative of the genus of fusion polypeptides encompassed by the instant claim.
The claims depend on a recited property, where the claim covers every conceivable structure for achieving the stated property, while the instant specification fails to describe any species with sufficient identifying characteristics such that one skill in the art could visualize or recognize the identity of the claimed subject matter. The specification fail to teach the structural identifying characteristics that are applicable to the genus.
The skilled artisan cannot envision the detailed chemical structure of the encompassed claimed molecules (if any) which have the activity without further testing, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of identification.
The scientific reasoning and evidence as a whole indicates that the objection should be maintained.
NEW CLAIM REJECTIONS/OBJECTIONS
Claim Objections
Claims 2-4, 6, 9, 11 and new claims 18-21 are objected to because of the following informalities:
Claims 2-4, 6, 9, 18-21 should be amended to recite, “The fusion polypeptide according to claim…”
Claims 11 and new claims 19-21 are objected to because of the interchangeable use of “Sequence ID NO:” and “SEQ ID NO:”. Amending the claims to recite one type of format, preferably “SEQ ID NO:”, would obviate this rejection.
Claim 19 is objected to because it should recite, “...comprises amino acid residues 32-396 of SEQ ID NO: 9.”
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph
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 11, 17, 20, and 21 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.
Claim 17 lacks antecedent basis. The instant claim should recite, “The fusion polypeptide according to claim 1…”.
Claims 20 and 21 lack antecedent basis. The instant claims should recite, “..wherein the fusion polypeptide comprises..”.
Claim 11 is indefinite because of the recitation, “..wherein the fusion polypeptide has an amino acid sequence..”. The word “an” is regarded as meaning "one". Thus, it is not clear if the claims read on peptide fragments (such as having one or two amino acids) or comprising the recited SEQ ID NO: sequence.
Amending claim 11 to recite, “..wherein the fusion polypeptide has the amino acid sequence..”, would obviate this rejection.
Potential allowable subject matter
As was stated in the previous Office Action, a search of the sequence data base failed to find prior art for SEQ ID NO: 1 and SEQ ID NO: 2.
Once the objection and the 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph are fixed, claim 11 would be allowed if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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.
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/R.M.D/Examiner, Art Unit 1647 4/20/2026
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647
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