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 .
Election/Restrictions
Applicant’s election without traverse of Group I and species of T2R which has the sequence of SEQ ID NO:7 and G protein which is Gα16gust44 in the reply filed on 05/22/2026 is acknowledged. On p. 10, lines 4-6, Gα16gust44 is identified as a promiscuous G protein and is not a species of promiscuous G protein encompassed by claim 3.
Claims 3 and 19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/22/2026.
The requirement is deemed proper and is therefore made FINAL.
Information Disclosure Statement
It is noted that in the IDS filed 5/20/2025, WO2013/072332 is a duplicate that was cited in the IDS of 11/01/2023, and WO2013/083044 is drawn to a “Gyroscopic System”.
Specification
The disclosure is objected to because of the following informalities: The first occurrence of an abbreviation should be accompanied by the full meaning. See p. 3, line 28, “MOI”.
Appropriate correction is required.
Claim Interpretation
It is noted that the specification on p. 5, lines 7-11, defines the term “or” as meaning for two things: comprising either or both. That is, it means not only one of a list of things, but includes a combination thereof.
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 2, 7, 18 and 19 and dependent claims 4-6 and 20 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 2 is indefinite for two reasons. First, it recites the “receptor is: a polypeptide sequence of SEQ ID NO:_...” However, receptors cannot be sequences. Instead, they can have a polypeptide sequence. That is, the sequence is a property of the receptor but not the receptor itself. Second, the claim further recites the “receptor is:…., of a functional fragment thereof…”, which does not make sense. It appears the word “or” may have been intended instead of “of”. This rejection could be obviated by, for example, using phrasing such as ‘… wherein the T2R bitter taste receptor is: a polypeptide having the sequence of SEQ ID NO:1, or a functional fragment thereof; a polypeptide having the sequence of SEQ ID NO:3, or ….’ or ‘wherein the T2R bitter taste receptor is: a polypeptide, the sequence of which is [or comprises or consists of—as appropriate] SEQ ID NO:1, or a functional fragment thereof;…NO:7, or a functional fragment thereof; or a ….’
Claim 7 is indefinite because it is unclear what the phrase “disposed on a solid support” means. Neither the phrase nor the word “disposed” is defined or used in the specification. It is unclear if “disposed” means, for example, ‘bound to’ or ‘destroyed by’. As a result, the metes and bounds of the claim are not clear. It is noted the specification (e.g., p. 3, line 3) uses the phrase, “adhered to a substrate”, the meaning of which is definite.
Claim 18 is indefinite because it recites the “receptor is: a polypeptide sequence of SEQ ID NO:_...” However, a receptor cannot be a sequence. Instead, it can have a polypeptide sequence. That is, the sequence is a property of the receptor but is not the receptor itself.
Claim 20 is indefinite because it recites the receptor is selected from one of SEQ ID Nos. 1, 5, 7 or 9. However, a receptor cannot be a sequence. Instead, it can have a sequence comprising or consisting of SEQ ID Nos. 1, 5, 7 or 9.
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.
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, 2, 4, 5, 7, 18 and 20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for an isolated U2OS cell comprising a T2R bitter taste receptor and a G protein, does not reasonably provide enablement for wherein the cell is not isolated. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is undue include, but are not limited to: 1) nature of the invention, 2) state of the prior art, 3) relative skill of those in the art, 4) level of predictability in the art, 5) existence of working examples, 6) breadth of claims, 7) amount of direction or guidance by the inventor, and 8) quantity of experimentation needed to make or use the invention. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The claims are drawn to a U2OS cell comprising a T2R bitter taste receptor and a G protein, wherein the receptor and G protein are functionally coupled. The specification only discloses use of such cells in vitro. Th U2OS cells are isolated and from a cell line. The prior art recognizes U2OS cells are kept only in cell culture, having originated from a human osteosarcoma tumor (e.g., Ames et al., Receptors Channels, 10:117-124, 2004, cited in the IDS filed 11/1/2023, p. 118, col. 1, first full paragraph). Neither the instant specification nor the prior art provides examples of using the cell in vivo, particularly as a cell transformed to express a bitter taste receptor and/or G protein. The instant specification does not provide direction or guidance about using such a cell that is not isolated, which includes as a part of a cell culture system and/or an in vitro assay. Even though the skill in the cell line art is high, use of cancer cell lines for other than in vitro assays or in tumor grafting experiments in preclinical cancer models is low. Use of transfected cells in a living system is complex and the results are often unpredictable at best. As a result, it would require undue experimentation to use the cells as claimed which are not isolated,.e.g,, in culture, in vitro, on a solid support.
Claims 2 and 18 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 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 specification discloses human T2R bitter taste receptors having the sequence of SEQ ID NO:1, 3, 5, 7, or 9. A T2R receptor having one of these sequences meets the written description provision of 35 USC 112(a). However, the claims are directed to or encompass a “functional fragment” of one of those receptors for which the full sequenced has been disclosed. First, what makes a fragment “functional” has not been disclosed, for example, whether it requires being immunogenic, coupling to a G protein, or binding a ligand. Second, no “functional fragments” have been disclosed. The only bitter taste receptors having support under the written description provision of 35 USC 112(a) are full length receptors having one of the above sequences. Also, the sole example of the specification is based on a full receptor that both binds a ligand and transduces a signal to the G protein. The skilled artisan cannot readily envisage the genus of functional fragments encompassed by the claims and applicant has not presented any such fragments.
The Written Description Guidelines for Examination of Patent Applications (MPEP § 2163) indicates, "The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice…, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical characteristics and/or other chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show applicant was in possession of the claimed genus…." [See MPEP § 2163(II)(A)(3)(a)(ii)] In the instant case, no actual reduction to practice supports the genus of functional fragment species. No identifying characteristics of or correlation between a functional fragment and an activity have been shown. It does not reasonably appear the inventors were in possession of the claimed genus.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111 (Fed. Cir. 1991), clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
Therefore, only a T2R bitter taste receptor, the sequence of which is SEQ ID NO:1, 3, 5, 7 or 9, but not the full breadth of the claim meets the written description provision of 35 U.S.C. § 112(a). Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. § 112 is severable from its enablement provision (see page 1115).
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.
Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 2, 4-7, 18 and 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Meyerhof et al. (Chem. Senses, 35:157-170, Adv. Pub. 2009, cited in the IDS filed 5/20/2025), US Patent 10,107,794 B2 (Kurash, cited in the PTO-892 mailed 4/1/2026) and Ames et al. (Receptors Channels, 10:117-124, 2004, cited in the IDS filed 11/1/2023) and US Patent 9,927,424 B2 (Radhakrishna).
Meyerhof et al. teaches a method testing bitter taste receptor response in a cell-based assay by transfecting HEK293T cells in culture with a plasmid comprising receptor hTAS2R (or T2R) and Gα16gust44 (p. 158, col. 2, second full paragraph, and sentence bridging pp. 157-158). “The chimeric G protein α subunit couples activated TAS2Rs to phospholipase C activity, inositol triphosphate and mobilization of intracellular calcium.” The negative control was HEK293T cells transfected to stably express Galpha16gust44 without the taste receptor. (ibid.) Meyerhof et al. report that 25 human bitter TAS2R receptors were known, e.g., hTAS2R7, -R4, -R10, -R14, -R16, -R38, -R40, -R43, -R44, and -R46, with some overlap in bitter taste sensitivity (p. 158, first full paragraph, and Tables 1-2). The transfected taste receptors coupled with the G protein were able to transmit a signal in response to certain chemical compounds that were potential ligands (Figs. 1-4 and Tables 1-2). Meyerhof et al. does not teach transfected cells which were U2OS cells or a bitter taste receptor having the sequence of instant SEQ ID NO:7.
Kurash teaches (col. 2, lines 30-36) human U2-OS cells were engineered to express sweet taste receptors and an α-gustducin and can be engineered to express T2R14 and an α-gustducin “using methods well known in the art.” Examples of α-gustducin that can be overexpressed in cells include, e.g., Ga15, Gα16gust25 and Gα16gust44 (col. 2, lines 36-48). Assays are taught using a test compound to identify a taste modulator, e.g., a molecule which blocks some or all of a bitter taste (col. 2, lines 60-64). Example 2, teaches transfection of cultured U2-OS cells with BacMam vector encoding Gα16gust44 (col. 8, lines 23-66). Other U2-OS cells were transfected with a vector for expression of T1R3/T1R2/Gα15 (col. 8, lines 28-32, and lines 50-55, and claims 1-2). It is taught the engineered cells can be modified to overexpress the sweet taste receptor and/or a G-protein, e.g., Gα16gust44 (col. 2, lines 20-23, and lines 37-40). An example of a cell-based assay in which U2-OS cells overexpressing Gα15 is presented in Examples 3 and 4 (see also claims 5 and 6).
Ames et al. state (p. 118, col.1, third paragraph), “As noted with reporter genes, we found that U-2 OS cells are highly susceptible to BacMam-mediated delivery of GPCRs.” Ames et al. showed different G protein-coupled receptors could be expressed in this U-2 OS engineered system (e.g., Figs. 3-5). It was “found U-2 OS cells are easily cultured and the transduced cells are firmly adherent to the high-density 384-well microtiter plates.” (p. 122, col. 2, second paragraph) “Furthermore, the combined use of BacMam and U-2 OS cells can significantly reduce the cell culture burden for groups supporting drug screening activities.” (p. 123, col. 2, first paragraph) On p, 123, col. 2, paragraph 2, Ames et al. state, “In most cases, though, we have found the U-2 OS cells to be very receptive to BacMam-mediated expression of GPCRs and we have been using them as heterologous hosts for many GPCRs either expressed alone or along with G proteins or G protein chimeras, as presented with the Gi-coupled M2 and M4 receptors. The fact that these cells are extremely receptive to BacMam mediated gene delivery, have very favorable growth characteristics, and are firmly adherent to plastic make them an attractive host for heterologous GPCR expression to support whole-cell-based functional GPCR assays.”
US Patent 9,927,424 B2 (Radhakrishna) teaches human T2R bitter taste receptors and assays for identifying compounds that modulate them. The sequence of receptor T2R39 is SEQ ID NO:40, which is the same as instant SEQ ID NO:7. The sequence of receptor T2R8 is SEQ ID NO:33, which is the same as instant SEQ ID NO:1. The sequence of receptor T2R10 is SEQ ID NO:35, which is the same as instant SEQ ID NO:3. The sequence of receptor T2R14 is SEQ ID NO:37, which is the same as instant SEQ ID NO:5. The sequence of receptor T2R46 is SEQ ID NO:46, which is the same as instant SEQ ID NO:9.(col. 22, lines 19-32) Radhakrishna discuss that different bitter taste receptors respond to different compounds (e.g., col. 24, lines 5-42). “The cells and cell lines comprising a bitter taste receptor, a mutant form thereof, or a naturally-occurring allelic variant thereof, can be used to identify modulators of bitter taste receptor function, including modulators that are specific for a particular bitter taste receptor mutant form or naturally-occurring allelic variant. The cells and cell lines can thus be used to obtain information about the properties, activities and roles of individual native or mutant forms or naturally-occurring allelic variants of bitter taste receptors and to identify bitter taste receptor modulators with activity for a particular native or mutant form or naturally-occurring allelic variant or for a subset of native or mutant forms or naturally-occurring allelic variants.” (col. 24, lines 53-65) Host cells used to express a receptor include U-2 OS (col. 24, lines 36-64). The cells and cell lines may further express a G protein, and they are complexed to produce an activity measurable by intracellular calcium concentration (col. 6, lines 58-67). This allows use of a cell-based assay to identify compounds that selective inhibit bitter taste induced by T2R agonists to make a product more palatable (Abstract and col. 1, lines 30-37). The cells and cell lines can be engineered to over-express the bitter taste receptor (col. 19, lines 10-30).
It would have been obvious to the artisan of ordinary skill to have transduced U2OS cells instead of HEK293 cells with a T2R bitter taste receptor, such as suggested by Kurash and Radhakrishna for use in expressing taste receptors coupled to G proteins and in view of the advantages that U2OS cells provide as taught by Ames et al. It further would have been obvious wherein the bitter taste receptor was a naturally occurring taste receptor such as T2R39 disclosed by Radhakrishna and used in the cell-based assay of Meyerhof et al. It alternatively would have been obvious wherein the use was in an assay with microtiter plates (a solid support), to which U2OS cells tightly adhere. It would have been obvious to overexpress the taste receptor and/or G protein in order to promote complexing of the two as well as supporting ligand-based receptor activity and subsequent measurable pathway activation (see Kurash, Meyerhof et al. and Radhakrishna). It would have been obvious to substitute in the experiments of Meyerhof et al. U2OS cells for the HEK293 cells for their disclosed advantages and to have use particular T2R bitter taste receptors in order to better understand and use the receptor characteristics, for example, to develop bitter T2R blocking agents that may make bitter food more palatable. The invention as claimed is prima facie obvious.
The Supreme court has acknowledged that (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 at 1390, U.S. 2007, emphasis added):
When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable varition..103 likely bars its patentability…if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person’s skill. A court must ask whether the improvement is more than the predictable use of prior-art elements according to their established functions… (at 1390)
…the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results (at 1395).
Examiner’s comment
The prior art relied upon in the rejection under 35 US 103 teaches bitter taste receptors with gustducin receptors and promiscuous G proteins G15 and G16gust25 (e.g., Kurash in col. 2, lines 37-48), which would have been obvious were the instant claim they are recited in (claim 3) not have been withdrawn due to not encompassing the elected species of G protein).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Claire Kaufman, whose telephone number is (571) 272-0873. Examiner Kaufman can generally be reached Monday through Friday 7am-3:30pm, Eastern Time.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa Ford, can be reached at (571) 272-0857.
Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
Official papers filed by fax should be directed to (571) 273-8300. NOTE: If applicant does submit a paper by fax, the original signed copy should be retained by the applicant or applicant's representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED so as to avoid the processing of duplicate papers in the Office.
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 .
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.
Claire Kaufman
/Claire Kaufman/
Primary Examiner, Art Unit 1674
August 28, 2026
Prosecution Insights