DETAILED ACTION
It is noted, the location and Examiner assigned to the instant application has changed. Please direct all further correspondence to Art Unit 1656 and the examiner signed below.
Notice of 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, claims 1-4 and 11-15 in the reply filed on 10 November 2025 is acknowledged. The requirement is deemed proper and therefore made Final.
Status of Application
Claims 1-21 are pending; Claims 5-10 and 16-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Thus, claims 1-4 and 11-15 are subject to examination on the merits.
Priority
The instant application is a 371 of PCT/CN2021/076314 filed 09 February 2021 which claims benefit of foreign priority document CN 202010098995.5 filed 18 February 2020 is acknowledged. Said document has been received.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03 March 2023 has been considered by the examiner. See initialed and signed PTO/SB/08.
Claim Rejections - 35 USC § 112(b)
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 3-4 and 11-15 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.
A. Claims 3-4 recite amino acid positions for specific mutation sites. However, these specific amino acid positions/mutations only make sense when one knows what the actual sequence of the protein is; here there is no structure/sequence defined at all. As such, these limitations render the claims indefinite.
B. Claim 4 is further deemed in definite because it is unclear if the “197/210” is the limitation intended or if this is a typographical error as claim 3 recites position “196/210” and because the specification does not have any limitation of position “197/210”. If it is a typographical error and the claim should recite “196/210”, it should be noted that this would end up in the claim not being further limiting (e.g. 112(d) issue). Clarification is requested.
C. Claims 13-15 are rejected as being indefinite. The claims are dependent upon claim 2, which recites SEQ ID NO: 1, or those polypeptides having 35% or more sequence identity thereto, which is thus inclusive of 100% sequence identity to SEQ ID NO: 1. The claims recite substitutions at positions S30, R96 and D177. However, the amino acid in SEQ ID NO: 1 at position 30 is not Serine, rather it is Glycine; the amino acid at position 96 is not Arginine, rather it is Valine; and the amino acid at position 177 is not Aspartate but rather Methionine. Thus, these amino acids as recited in the claims are deemed to not have antecedent basis in SEQ ID NO: 1 and are indefinite.
Claim Rejections - 35 USC § 112(a)
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.
Claims 1-4 and 11-15 are rejected under 35 U.S.C. 112(a) 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 had possession of the claimed invention.
The MPEP in section 2163(I) states that the purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made/filed, of the specific subject matter claimed:
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonable conclude the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. However, a showing of possession alone does not cure the lack of a written description. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 969-70, 63 USPQ2d 1609, 1617 (Fed. Cir. 2002). For example, it is now well accepted that a satisfactory description may be found in originally-filed claims or any other portion of the originally-filed specification. See In re Koller, 613 F.2d 819, 204 USPQ 702 (CCPA 1980); In re Gardner, 475 F.2d 1389, 177 USPQ 396 (CCPA 1973); In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). However, that does not mean that all originally-filed claims have adequate written support. The specification must still be examined to assess whether an originally-filed claim has adequate support in the written disclosure and/or the drawings.
PNG
media_image1.png
18
19
media_image1.png
Greyscale
An applicant shows that the inventor was in possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997)"
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398 (Fed. Circ. 1997).
MPEP § 2163 further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence." Furthermore, the courts have also held that possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895.
The instant claims are drawn to an optical sensor comprising an arginine sensitive polypeptide and an optically active polypeptide which is located within a sequence of the arginine sensitive polypeptide, as defined in the specification at paragraph 0054, PG-Pub. There is no specific structure/sequence for the arginine sensitive polypeptide (with the exception of claim 2, however, sequence identity as low as 35% has issues with regard the enormous genus of polypeptides encompassed by that low of sequence identity and how it relates to the expected structure/function), and none for the optically active polypeptide. Thus, said proteins can be from any species, be fragments, variants of the naturally occurring polypeptides making the genus of fusion polypeptides enormous, variable and unpredictable in terms of structure and/or function. The specification, however, only utilizes for the optically active polypeptides circular permuted green or yellow fluorescent proteins; and for the arginine-sensitive polypeptide arginine-binding protein STM4351 derived from Salmonella Typhimurium comprising SEQ ID NO: 1. These specific examples are not representative of the entire genus of fusion proteins in terms of structure and function.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1 is rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Marvin et al. (US 20150111222 – cited herein).
Marvin et al. teach fusion proteins comprising a framework portion that is a periplasmic binding protein (PBP) further having a signaling portion that is a circularly permuted fluorescent protein (cpFP) inserted into the (PBP), and wherein the PBP is selected from those including arginine binding protein – See claims 1, 8, 14-15, paragraphs 0095-0097, 105-110; 0114-0118, 0126-0128.
PNG
media_image2.png
166
416
media_image2.png
Greyscale
Although the paragraphs 0110 and 0128 describe multiple, alternative PBP’s inclusive of arginine binding proteins, the disclosure of ‘arginine binding proteins ' is one of only 16 alternative embodiments and therefore, one of ordinary skill would have immediately envisaged such a fusion protein comprising an arginine binding protein as the PBP framework portion and having a cpFlourescent protein within said arginine binding protein sequence. Thus, the disclosure of Marvin et al. is taken as anticipatory over the claimed invention.
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.
Claim(s) 2-4 and 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Marvin et al. (US 20150111222 – cited herein) as applied to claim 1 above, and further in view of Stamp et al. (Proteins: Structure, Function and Bioinformatics – July 2011 – cited on IDS of 03/03/2023).
The teachings of Marvin et al. are described above and incorporated into the instant rejection. Marvin et al. further teach methods of identifying insertion sites for the cpFP into the PBP based upon the crystal structures. They also teach several PBP crystal structures in both open and closed conformations and their insertion sites (See Figures 1-5). Specifically they teach:
[0175] Methods herein provide systematic and generic approaches for the design and production of genetically encoded recombinant peptides containing an analyte-binding framework portion linked (e.g., operably linked) to a signaling portion, wherein the signaling portion is allosterically modulated or regulated by the framework portion upon interaction of the framework portion with an analyte. Generally, methods include: (i) selecting one or more target analytes; (ii) selecting a framework portion (e.g., a PBP) that interacts with (e.g., interacts specifically with) or binds to (e.g., binds specifically to) the target analyte and that undergoes a conformational change upon interacting with or binding to the analyte; (iii) identifying sites or amino acid positions within the framework portion (e.g., the PBP) where the conformational change occurs; and (iv) inserting or cloning a signaling portion into the site or amino acid position identified in (iii). Methods can, optionally, further include: (v) modifying or optimizing linker sequences between the framework portion and the signaling portion, for example, by genetic manipulation (e.g., by point mutation); (vi) modifying or optimizing analyte binding; (vii) modifying the signal generated by the biosensor; and/or (viii) cloning the biosensor into a suitable vector.
[0176] In some instances: (iii) includes identification of insertion sites by analysis of the structure (e.g., crystal structure) of the selected framework portion (e.g., the selected PBP) in one or both of its open and closed states to determine amino acid positions at which analyte-binding dependent structural changes occur. In instances where structures for both open and closed states are not available, analysis can be conducted by analogy to a structurally similar framework portion (e.g., PBP); (iv) includes cloning a signaling portion (e.g., a cpFP) at the site identified in (iii) such that the analyte-binding dependent structural change observed in (iii) will result in a conformational change in the signaling portion (e.g., the cpFP) and allosteric modulation of the signaling portion; (v) includes generating a library of mutants of biosensors with distinct linker sequences (e.g., by point mutation), screening the library of mutants to identify mutants with enhanced properties (e.g., improved signal-to-noise ratio), and selecting mutants with enhanced properties (e.g., improved signal-to-noise ratio); (vi) includes increasing or decreasing binding or affinity of the framework portion to the analyte, e.g., by modifying amino acids in the interacting face of the framework portion or regions within the framework portion that are critical for analyte binding; (vii) includes increasing or decreasing signal emission by the signaling portion and/or changing the color of the signal where the signaling portion is a FP (e.g., a cpFP). Methods including (i)-(viii) are exemplified in the Examples section herein.
Marvin et al., however, do not teach the exact arginine binding protein to utilize (claim 2), nor the exact insertion sites (claims 3-4 and 11-12).
Stamp et al. teach the crystal structure of the periplasmic binding protein STM4351 which is an arginine binding protein from Salmonella typhimurium, wherein the structure is of the closed structure (e.g. when arginine is bound) – See entire document. The sequence of STM4351 is disclosed in Figure 1 and has 100% sequence identity to instant SEQ ID NO: 1 (See Figure 1 and also Supplemental Content, 20251208_134516_us-17-904-498a-1.rup file, Duplicates for Result #2). Stamp et al. teach that the structure of STM4351 is “typical of group I PBP.”, and Lobe 1 comprises 121 amino acids (aa1-84 and 186-223) and Lobe 2 has 88 amino acids (aa90-178) – See p. 2355, 2nd col., 2nd paragraph.
Therefore it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to utilize STM4351 comprising SEQ ID NO: 1 as the periplasmic binding protein (PBP) analyte framework portion, because Marvin et al. suggest a PBP arginine binding protein as an analyte framework protein and Stamp et al. teach the specific protein and crystal structure of STM4351 is a typical PBP. In addition, it would be obvious to one of ordinary skill in the art to determine the insertion site of the cpFP protein and its specific locations based upon the methodology as disclosed by Marvin et al. (See paragraphs 0175-0176 as above), and based upon the specific crystal structure of Stamp et al., as well as the other typical PBP crystal structures in Marvin et al. (See Examples). One skilled in the art would be motivated to utilize STM4351 comprising SEQ ID NO: 1 of Stamp et al. as the arginine binding protein in Marvin et al. because the crystal structure is known and provides guidance for the insertion sites of cpFP. One skilled in the art would have a reasonable expectation of success in utilizing the crystal structure and sequence of Stamp et al. in the fusion protein of Marvin et al. and to arrive at the specific claimed insertion sites because Marvin et al. provide step-by-step guidance for a skilled artisan to select multiple insertion sites and how to test each one (See Examples; paragraphs 0175-0176).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUZANNE M NOAKES whose telephone number is (571)272-2924. The examiner can normally be reached M-F (7-4).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached at 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656 09 December 2025