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 .
Response to Amendment
Applicant’s amendment filed 05/12/2026 is acknowledged. Claims 7 and 8 are amended and claims 1-3 are canceled. Claims 4-6 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 7 and 8 are under examination.
Drawings
The drawings were received on 05/12/2026. The issue regarding color drawing set forth at pages 2-4 in the Office action mailed 02/12/2026 is overcome.
The drawings filed 05/12/2026 are objected to, however, because the labeling in Figures 4B, 5B-I, 6A-E, 7A-I, 8A and 9A-G is difficult to read. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Rejections Withdrawn
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Any previous rejection over claims 1-3 are hereby withdrawn in response to Applicant’s cancelation of those claims.
Claim Rejections - 35 USC § 102
The rejection of claims 7 and 8 under 35 U.S.C. 102(a)(1) as being anticipated by Chauhan et al. (Biol. Reprod (2009); 81: 777-783) is withdrawn in response to Applicant’s amendment deleting any reference to compositions for measuring mRNA expression levels of adrenomedullin 2 (ADM2) comprising a primer, probe or antisense oligonucleotide. While Chauhan et al. disclose a an ADM2 antibody for measuring protein (see p. 778, right column, 1st full paragraph and Figure 2; p. 779, Figure 3; p. 780, Figure 4), they do not disclose all of the elements of the protein chip kit in amended claim 7.
The rejection of claims 7 and 8 under 35 U.S.C. 102(a)(1) as being anticipated by Sproul et al. (WO2014100737) is withdrawn in response to Applicant’s amendment deleting any reference to compositions for measuring mRNA expression levels of adrenomedullin 2 (ADM2) comprising a primer, probe or antisense oligonucleotide.
The rejection of claim 7 under 35 U.S.C. 102(a)(1) as being anticipated by Hollander et al. (Journal of Surgical Research 197 (2015) 219-224) is withdrawn in response to Applicant’s amendment deleting any reference to compositions for measuring mRNA expression levels of adrenomedullin 2 (ADM2) comprising a primer, probe or antisense oligonucleotide. While Hollander teach measuring adrenomedullin 2 (ADM2) protein levels with an antibody (see p. 220, right column under “2.2 Immunohistochemistry” and p. 222, Figure 1 and Table 2), they do not disclose all of the elements of the protein chip kit in amended claim 7.
Claim Interpretation
Amended claim 7 contains written instructions (printed matter). To be given patentable weight, the printed matter and associated product must be in a functional relationship (see MPEP 2111.05(I)(A). Evidence against a functional relationship exits where the printed matter and product do not depend upon each other, then no functional relationship exists. For example, in a kit containing a set of chemicals and a printed set of instructions for using the chemicals, the instructions are not related to that particular set of chemicals. In re Ngai, 367 F.3d at 1339, 70 USPQ2d at 1864. See MPEP 2111.05(I)(B). In the instant case, the written instructions recited in claim 7 are not given patentable weight.
The claims are drawn to a kit, and are thus drawn to a product of manufacture. The claims recite an intended use for the kit (“for diagnosis or prognosis prediction of thyroid cancer” in claim 7). According to MPEP 2111.02(II), “[t]he claim preamble must be read in the context of the entire claim” and that “[d]uring examination, statements in the preamble reciting the purpose or intended use of the claimed invention must be evaluated to determine whether or not the recited purpose or intended use results in a structural difference (or, in the case of process claims, manipulative difference) between the claimed invention and the prior art.
If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction.
In the instant case, the body of the claims set forth all the limitations of the claimed invention, whereas the preamble merely sets forth the intended use of the claimed products.
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 7 and 8 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 7 is drawn to a product of manufacture, but recites a “protein chip kit…wherein the ADM2 protein level is determined by an absolute concentration in μg/mL or a relative signal intensity.” The final wherein clause in claim 7 is confusing because it suggests a method step is carried out. See MPEP 2173.05(p)(II), which instructs that a single claim which claims both an apparatus and the method steps of using the apparatus is indefinite under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph, citing In re Katz Interactive Call Processing Patent Litigation, 639 F.3d 1303, 1318, 97 USPQ2d 1737, 1748-49 (Fed. Cir. 2011), IPXL Holdings v. Amazon.com, Inc., 430 F.3d 1377, 1384, 77 USPQ2d 1140, 1145 (Fed. Cir. 2005), and Ex parte Lyell, 17 USPQ2d 1548 (Bd. Pat. App. & Inter. 1990).
For the sake of applying prior art, the wherein clause is interpreted as being a part of the written instructions.
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 7 and 8 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 claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Claim 7 recites a protein chip kit comprising: (a) an ADM2-capture reagent comprising an antibody or an aptamer that specifically binds ADM2 protein; (b) a matrix selected from a 96-well plate made of polyvinyl resin and a 96-well plate made of polystyrene resin; (c) a suitable buffer solution and (d) a secondary antibody labeled with a coloring enzyme selected from peroxidase and alkaline phosphatase;(e) a coloring substrate selected from ABTS, OPD, and TMB. The instant specification describes the elements recited in claim 7 at the paragraph bridging pates 14-15:
When the kit of the present invention may be a kit for measuring the expression level of ADM2 protein, it may include a matrix, a suitable buffer solution, a coloring enzyme, or a secondary antibody labeled with a fluorescent substance, a coloring substrate or the like for the immuno-logical detection of antibody. As for the matrix, a nitrocellulose membrane, a 96 well plate made of polyvinyl resin, a 96 well plate made of poly-styrene resin, and a sliding glass may be used. As for the coloring enzyme, peroxidase and alkaline phosphatase may be used. As for the fluorescent substance, fluorescein isothiocyanate (FITC) and rhodamine B isothiocyanate (RITC) may be used. As for the coloring substrate solution, ABTS(2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid)), OPD(O-phenylenediamine), or TMB (tetramethylbenzidine) may be used.
The elements recited in the claim and disclosed at the paragraph bridging pages 14-15 are common components of enzyme-linked immunosorbent assays (ELISAs). See for instance, the review by John E. Butler (Journal of Immunoassay, 2000; 21:2-3: 165-209), on ELISAs, which discloses elements of claim 7, including the 96 well polystyrene microtiter plate, primary and secondary antibodies, peroxidase and TMB (see, for example, p. 168, Figure 2; pages 177-179; p. 182, Table 3).
The instant specification discloses the “protein chip” broadly at the paragraph bridging pages 12-13 as part of a list of different methods for measuring ADM2 protein:
In the present invention, the term “measuring the expression level of protein” is a process for confirming the presence and expression level of a protein expressed in a thyroid cancer marker gene (ADM2) from a biological sample for the diagnosis or prognosis prediction of thyroid cancer and may be performed by generally identifying the protein amount. Analysis methods for this may include, but not limited to, western blot, enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), radioimmunodiffusion, Ouchterlony immunodiffusion, rocket immuno-electrophoresis, immunohistochemistry, immunoprecipitation assay, complement fixation assay, fluorescence activated cell sorting (FACS), protein chips and the like. (Emphasis added by Examiner).
The art teaches protein chips that comprise Surface Enhanced Laser Desorption/ Ionization (SELDI) technology, which allows for the measurement of many different proteins at once (see the Product Note from Ciphergen (2004), available at ProteinChip+technology+(Ciphergen+Biosystems; 8 pages total). In addition, Liu et al. (Biosensors and Bioelectronics 96 (2017) 332-338) teach an ELISA-Chip comprising “three layers of PMMA [poly(methyl methacrylate)] ELISA-Chip” (see p. 334, Figure 1; p. 335, left column, 1st paragraph). Similarly, Hu et al. (ACS Nano. 2010 Jan;4(1):488-494. DOI: 10.1021/nn901404h. PMID: 20041634) describe a microfluidic protein chip used in conjunction with a sandwich immunoassay (see p. 491, Figure 4).
There is no explicit, implicit or inherent support for a protein chip kit that comprises the elements of an ELISA. The Federal Circuit has pointed out that, under United States law, a description that merely renders a claimed invention obvious may not sufficiently describe the invention for the purposes of the written description requirement of 35 U.S.C. 112 (see Eli Lilly, 119 F.3d at 1567, 43 USPQ2d at 1405). In other words, “[e]ntitlement to a filing date does not extend to subject matter which is not disclosed, but would be obvious over what is expressly disclosed.” See MPEP 2163.02, which cites Lockwood v. American Airlines Inc., 41 USPQ2d 1961 (Fed. Cir. 1977).
Lockwood argues that the district court erred by looking solely at the applications themselves. We do not agree. It is the disclosures of the applications that count. Entitlement to a filing date does not extend to subject matter which is not disclosed, but would be obvious over what is expressly disclosed. It extends only to that which is disclosed. While the meaning of terms, phrases, or diagrams in a disclosure is to be explained or interpreted from the vantage point of one skilled in the art, all the limitations must appear in the specification. The question is not whether a claimed invention is an obvious variant of that which is disclosed in the specification. Rather, a prior application itself must describe an invention, and do so in sufficient detail that one skilled in the art can clearly conclude that the inventor invented the claimed invention as of the filing date
sought. See Martin v. Mayer, 823 F.2d 500, 504, 3 USPQ2d 1333, 1337 (Fed.Cir. 1987) (stating that it is “not a question of whether one skilled in the art might be able to construct the patentee's device from the teachings of the disclosure…Rather, it is a question whether the application necessarily discloses that particular device.”) (quoting Jepson v. Coleman, 314 F.2d 533, 536, 136 USPQ 647, 649-50 (CCPA 1963)). Lockwood argues that all that is necessary to satisfy the description requirement is to show that one is “in possession” of the invention. Lockwood accurately states the test, see Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed.Cir. 1991), but fails to state how it is satisfied. One shows that one is “in possession” of the invention by describing the invention, with all its claimed limitations, not that which makes it obvious. Id. (“[T]he applicant must also convey 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.”) (emphasis in original). One does that by such descriptive means as words, structures, figures, diagrams, formulas, etc., that fully set forth the claimed invention. Although the exact terms need not be used in haec verba, see Eiselstein v. Frank, 52 F.3d 1035, 1038, 34 USPQ2d 1467, 1470 (Fed.Cir. 1995) (“[T]he prior application need not describe the claimed subject matter in exactly the same terms as used in
the claims...”), the specification must contain an equivalent description of the claimed subject matter. A description which renders obvious the invention for which an earlier filing date is sought is not sufficient.
While it may be obvious to adapt a teaching of the elements of an ELISA assay to a protein chip, the protein chip recited in the claims is different in scope than the generic “protein chip” disclosed in the instant specification, and therefore, constitutes new matter.
Notice for all US Patent Applications filed on or after March 16, 2013: 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 7 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Panda et al. (WO2017077499) in view of John E. Butler (Journal of Immunoassay, 21:2-3, 165-209) and Liu et al. (Biosensors and Bioelectronics 96 (2017) 332-338). The first factor to consider when making a rejection under 35 U.S.C. 103(a) is to determine the scope and contents of the prior art. Panda et al. disclose kits and methods for measuring a group of 38 proteins, including adrenomedullin 2 (ADM2), as predictive/prognostic markers for head and neck cancer, for instance by ELISA (see p. 24, lines 18-34). The second factor to consider is to ascertain the differences between the prior art and the instant claims. Panda et a. do not teach the elements of the kit, nor do they disclose a “protein chip” kit.
Regarding the components of the kit, Butler discloses assays comprising the elements of claims 7 and 8, including the 96-well polystyrene microtiter plate, primary and secondary antibodies, suitable buffers, peroxidase and TMB (see, for example, p. 168, Figure 2; paragraph bridging pages 170-171; pages 177-179; p. 182, Table 3), which were well-known in the art. Regarding a protein chip assay, Liu et al. disclose a “fully integrated distance readout ELISA-Chip for point-of-care testing”, which combines a microfluidic chip with an ELISA (see title/abstract; p. 334, Figure 1). It would have been obvious to the person of ordinary skill in the art at the time the of the filing of the invention to modify the teachings of Panda et al. by adapting the ELISA to a multiplex protein testing kit because they teach measuring 38 proteins and Liu et al. teach that their system is “suitable for automation and multiplexing” (see p. 338, left column, 1st paragraph). The person of ordinary skill in the art would have been motivated to streamline this process because running individual assays would be time-consuming and expensive and Liu teach their ELISA-Chip is less expensive than running individual ELISAs and suitable in the field for point-of-care (see p. 338, left column, 2nd paragraph). Furthermore, the person of ordinary skill in the art could have reasonably expected success because Liu et al. teach (p. 338, left column, last paragraph):
The ELISA-Chip method showed high specificity, good intra-assay (CV, 6.5%) and inter-assay precision (CV, 9.1%). Additionally, the reliable detection of CRP in 16 real patients' samples have validated the potential application of ELISA-Chip in POC diagnostics. Furthermore, the ELISA-Chip system is highly applicable as a sandwich-based platform for the detection of a variety of protein biomarkers. With the advantages of equipment-free, visual analysis, easy operation, high sensitivity, and low cost, the integrated sample-in-answer-out ELISA-Chip with distance readout shows great potential for quantitative POCT in resource-limited settings.
Thus, the claims do not contribute anything non-obvious over the prior art.
Conclusion
No claim is allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Grogan et al. (Cancers 2010, 2, 885-912; doi:10.3390/ cancers2020885) teach the advantage of using multiple biomarkers in thyroid cancer diagnosis (see whole document).
THIS ACTION IS MADE FINAL. 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 CHRISTINA M BORGEEST whose telephone number is (571)272-4482. The examiner can normally be reached M-F 9-5:30 EDT.
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, Jeffrey Stucker can be reached at 5712720911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHRISTINA M BORGEEST/Primary Examiner, Art Unit 1675
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