A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 5/28/2026 has been entered.
DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Claim filed on 1/22/2026 is acknowledged.
3. Claims 2-11, 15-18 and 26-32 have been cancelled.
4. Claims 1, 12-14 and 19-25 are pending in this application.
5. The withdrawn claims 19-23 have been rejoined; and the restriction requirement between Group 1 and Group 3 as set forth in the Office action mailed on 2/13/2025 has been withdrawn in the previous office action.
6. Information disclosure statements (IDS) filed on 5/28/2026 has been considered by the Examiner.
7. The instant claims 1, 12-14 and 19-25 are drawn to a system comprising: a first polypeptide comprising a first alpha helix forming amino acid sequence configured to bind a second alpha helix forming amino acid sequence linked by a first flexible linker peptide, and a second polypeptide comprising a third alpha helix forming amino acid sequence configured to bind a fourth alpha helix forming amino acid sequence linked by a second flexible linker peptide; wherein the first alpha helix forming amino acid sequence and the third alpha helix forming amino acid sequence are configured to form a coiled coil when the first alpha helix forming amino acid sequence is unbound from the second alpha helix forming amino acid sequence, and the second alpha helix forming amino acid sequence and the fourth alpha helix forming amino acid sequence are configured to form a coiled coil when the third alpha helix forming amino acid sequence is unbound from the fourth alpha helix forming amino acid sequence; wherein the first polypeptide comprises the amino acid sequence that is at least 95% identical to any one selected from the group consisting of SEQ ID NOs: 42-73, and the second polypeptide comprises the amino acid sequence that is at least 95% identical to any one selected from the group consisting of SEQ ID NOs: 42-73; and wherein the amino acid sequences of the first polypeptide and the second polypeptide are different; and a method for analyte detection comprising: (a) mixing a sample containing an analyte with a test solution, wherein the test solution comprises: a first polypeptide comprising a first alpha helix forming amino acid sequence configured to bind a second alpha helix forming amino acid sequence linked by a first flexible linker peptide, and a second polypeptide, comprising a third alpha helix forming amino acid sequence configured to bind a fourth alpha helix forming amino acid sequence linked by a second flexible linker peptide; wherein the first alpha helix forming amino acid sequence and the third alpha helix forming amino acid sequence are configured to form a coiled coil when the first alpha helix forming amino acid sequence is unbound from the second alpha helix forming amino acid sequence, and the second alpha helix forming amino acid sequence and the fourth alpha helix forming amino acid sequence are configured to form a coiled coil when the third alpha helix forming amino acid sequence is unbound from the fourth alpha helix forming amino acid sequence; wherein the first polypeptide comprises the amino acid sequence that is at least 95% identical to any one selected from the group consisting of SEQ ID NOs: 42-73, and wherein the second polypeptide comprises the amino acid sequence that is at least 95% identical to any one selected from the group consisting of SEQ ID NOs: 42-73, and wherein the amino acid sequence of the first polypeptide and the second polypeptide are different; wherein a first signal generation component is operably linked to the first polypeptide and a second signal generation component is operably linked to the second polypeptide; and wherein a first analyte binding component operably linked to the first polypeptide and a second analyte binding component operably linked to the second polypeptide configured to promote formation of a dimer upon analyte binding; and (b) detecting a signal. A search was conducted on the elected species; and this appears to be free of prior art. A search was extended to the genus in claims 1 and 19; and these too appear to be free of prior art. Claims 1, 12-14 and 19-25 are examined on the merits in this office action.
Please note: After further careful reconsideration, a non-final office action is issued hereby.
New Rejections
Claim Rejections - 35 U.S.C. § 112 paragraph (a)
Written Description
8. The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
9. Claims 19-23 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient” (MPEP § 2163).
A claimed genus may be satisfied through sufficient description of a representative number of species or disclosure of relevant, identifying characteristics such as functional characteristics coupled with a known or disclosed correlation between function and structure (MPEP § 2163(3)a(II)). The number of species that describe the genus must be adequate to describe the entire genus; if there is substantial variability, a large number of species must be described.
The analysis for adequate written description considers (a) actual reduction to practice, (b) disclosure of drawings or structural chemical formulas, (c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure, and (d) representative number of samples.
In the instant case, claims 19-23 are drawn a method for analyte detection comprising: (a) mixing a sample containing an analyte with a test solution, wherein the test solution comprises: a first polypeptide comprising a first alpha helix forming amino acid sequence configured to bind a second alpha helix forming amino acid sequence linked by a first flexible linker peptide, and a second polypeptide, comprising a third alpha helix forming amino acid sequence configured to bind a fourth alpha helix forming amino acid sequence linked by a second flexible linker peptide; wherein the first alpha helix forming amino acid sequence and the third alpha helix forming amino acid sequence are configured to form a coiled coil when the first alpha helix forming amino acid sequence is unbound from the second alpha helix forming amino acid sequence, and the second alpha helix forming amino acid sequence and the fourth alpha helix forming amino acid sequence are configured to form a coiled coil when the third alpha helix forming amino acid sequence is unbound from the fourth alpha helix forming amino acid sequence; wherein the first polypeptide comprises the amino acid sequence that is at least 95% identical to any one selected from the group consisting of SEQ ID NOs: 42-73, and wherein the second polypeptide comprises the amino acid sequence that is at least 95% identical to any one selected from the group consisting of SEQ ID NOs: 42-73, and wherein the amino acid sequence of the first polypeptide and the second polypeptide are different; wherein a first signal generation component is operably linked to the first polypeptide and a second signal generation component is operably linked to the second polypeptide; and wherein a first analyte binding component operably linked to the first polypeptide and a second analyte binding component operably linked to the second polypeptide configured to promote formation of a dimer upon analyte binding; and (b) detecting a signal.
The genus of instant claimed first analyte binding component and/or second analyte binding component is extremely broad, including any moiety that can bind to any analyte.
The instant specification discloses an ScFV, a Fab, an antibody, a natural analyte binding domain, and a synthetic analyte binding domain as examples of analyte binding domain.
The instant specification further discloses that analyte binding increases the concentration of the two polypeptides, resulting in an increased rate of conformational switching to form an intermolecular interaction between the alpha helices in the two polypeptides, stabilizing the complex.
The issue at question is whether a person of ordinary skilled in the art would be able to determine what structural feature is required for a moiety to have the functional characteristics of being first analyte binding component and/or second analyte binding component; and such analyte binding components configured to promote formation of a dimer upon analyte binding.
(a) actual reduction to practice and (b) disclosure of drawings or structural chemical formulas:
In the instant case, the instant specification discloses an ScFV, a Fab, an antibody, a natural analyte binding domain, and a synthetic analyte binding domain as examples of analyte binding domain.
The instant specification further discloses that analyte binding increases the concentration of the two polypeptides, resulting in an increased rate of conformational switching to form an intermolecular interaction between the alpha helices in the two polypeptides, stabilizing the complex.
There is no an analyte binding component being tested in the working examples in instant specification.
Taken all these together, other than the limited examples, the instant specification fails to disclose what structural feature is required for a moiety to have the functional characteristics of being first analyte binding component and/or second analyte binding component; and such analyte binding components configured to promote formation of a dimer upon analyte binding.
(c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure:
As discussed above, in the instant case, based on the disclosure of instant specification, other than the limited examples, a person of ordinary skilled in the art would not be able to determine what structural feature is required for a moiety to have the functional characteristics of being first analyte binding component and/or second analyte binding component; and such analyte binding components configured to promote formation of a dimer upon analyte binding.
With regards to a moiety capable of binding to anything, the art is unpredictable, as discussed in Lowe (2022, pages 1-6, from https://www.science.org/content/blog-post/not-alphafold-s-fault) and many others. Lowe explicitly states that “the number of strong binding interactions predicted is basically the same between the active compounds and the inactive ones” (see page 2, the 2nd paragraph).
With regards to protein/protein interactions, in particular, coiled-coil interactions, Potapov et al (PLoS Comput Biol, 2015, 11(2): e1004046, pages 1-28, filed with IDS), throughout the literature, teach design model to predict coiled-coil interactions, for example, Title; and Abstract. Potapov et al explicilty state that “Rational protein-interaction design has been approached in many ways over the past decades, but it remains a challenge”; and “Understanding the detailed relationship between protein sequences and their interactions is an outstanding challenge in protein science. So far, predicting these relationships accurately using purely computational models has not been practical for most system”, for example, pages 1-2, Section “Author Summary”; and page 14, the 1st paragraph in Section “Discussion”. The unpredictability of coiled-coil interactions is further discussed in Truebestein et al (Bioessays, 2016, 38, pages 903-916, cited and enclosed in the previous office action).
Therefore, based on the state of art, a person of ordinary skilled in the art would not be able to determine what structural feature is required for a moiety to have the functional characteristics of being first analyte binding component and/or second analyte binding component; and such analyte binding components configured to promote formation of a dimer upon analyte binding.
(d) representative number of samples:
In the instant case, the genus of instant claimed first analyte binding component and/or second analyte binding component is extremely broad, including any moiety that can bind to any analyte.
And, as discussed in (a) and (b) above, the instant specification discloses an ScFV, a Fab, an antibody, a natural analyte binding domain, and a synthetic analyte binding domain as examples of analyte binding domain.
The instant specification further discloses that analyte binding increases the concentration of the two polypeptides, resulting in an increased rate of conformational switching to form an intermolecular interaction between the alpha helices in the two polypeptides, stabilizing the complex.
There is no an analyte binding component being tested in the working examples in instant specification.
Considering the broadness of the genus of instant claimed first analyte binding component and/or second analyte binding component, the instant specification fails to provide sufficient examples to describe the entire genus of first analyte binding component and/or second analyte binding component; and such analyte binding components configured to promote formation of a dimer upon analyte binding claimed.
Taken all these together, considering the state of the art and the disclosure in instant specification, it is deemed that the instant specification fails to provide adequate written description for the claimed genus of first analyte binding component and/or second analyte binding component; and such analyte binding components configured to promote formation of a dimer upon analyte binding; and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Examiner’s Notes
10. As stated in the previous office action, the system and method of using system recited in instant claims 1, 12-14 and 19-25 are free of prior art. The closest prior art is Betz et al (Biochemistry 1997, 36, pages 2450-2458, cited and enclosed in the previous office action). The teachings of Betz et al have been set forth in Section 30 of the Non-final office action dated 8/13/2025. However, there is no teaching, motivation, or other type of suggestion to modify the system in Betz et al and arrive at the system and method of using system recited in instant claims 1, 12-14 and 19-25. Therefore, the system and method of using system recited in instant claims 1, 12-14 and 19-25 are both novel and unobvious over the prior arts of record. And the claimed system is markedly different from what exist in nature.
Conclusion
Claims 1, 12-14 , 24 and 25 are allowed. Claims 19-23 are rejected.
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/LI N KOMATSU/Primary Examiner, Art Unit 1658
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