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 .
Priority
Acknowledgment is made of applicant's claim for foreign priority under 35 USC 119(a)-(d). Receipt of the certified copies of the foreign priority documents, KR 10-2020-0184113 filed on 12/28/2020, KR 10-2021-0109598 filed on 8/19/2021, and 10-2021-0169688 filed on 12/01/2021, is acknowledged. These papers have been placed of record in the file.
Status of the Claims
Claims 1-20 are pending and examined herein.
Withdrawn Objections/Rejections
Objections to the specification is withdrawn in view of Applicant’s amendment to correct grammatical errors.
The rejection of claims 1-19 under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more is withdrawn in view of Applicant’s arguments/amendments.
The rejection of claims 1-20 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph is withdrawn in view of Applicant’s amendments/arguments.
The rejection of claims 1-3, 13-16, 19-20 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Gouda et al is withdrawn in view of Applicant’s amendments and arguments.
The rejection of claims 1, 2, 6, 7, 13, 14 and 16-20 under 35 U.S.C. 102(a)(1) as being anticipated by Goode et al. is withdrawn in view of Applicant’s amendments and arguments.
The rejection of claims 1-4, 6, 13, 18-20 under 35 U.S.C. 102(a)(1) as being anticipated by Yi et al. is withdrawn in view of Applicant’s amendments and arguments.
The rejection of claims 4-12 under 35 U.S.C. 103 as being unpatentable over Gouda et al in view of Atherton et al is withdrawn in view of Applicant’s amendment and arguments.
The rejection of claims 17-18 under 35 U.S.C. 103 as being unpatentable over Gouda et al in view of Mora-Sanz et al is withdrawn in view of Applicant’s amendment and arguments.
New Rejections
Claim Rejections - 35 USC § 112
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 1-20 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. This is a New Matter rejection.
Amended claims 1, 14 and 16 recite a method of generating a chemical catalyst or a sensor. This recitation is not supported by the specification as originally filed. While the specification does recite catalyst, it does not specifically disclose a method of making or using “chemical catalyst” nor does it disclose a method of making or using “a sensor”. Nowhere in the specification is there a mention of the term “chemical catalyst” or “sensor” as claimed.
Therefore, claims 1-20 are not supported by the specification as originally filed.
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.
Claims 1, 2, 13 and 17-20 are rejected under 35 U.S.C. 102(a)(2) as being clearly anticipated by Niemeyer et al (Covalent DNA--Streptavidin Conjugates as Building Blocks for Novel Biometallic Nanostructures. Angew. Chem. Int. Ed. 1998, 37, No. 16. PP 2265-2268.)
Claims are broadly directed to a method of generating (i.e. making) a catalyst by conversion and synthesis of materials via biostructure by selecting a bio-template based on its shape, labeling the biostructure template with antibody conjugated to inorganic particles.
With respect to claim 1, Neimeyer discloses covalent DNA-streptavidin conjugates as building blocks for novel biometallic nanostructures. Neimeyer discloses generation of nanoscale structural and functional devices by self-assembly of small molecular building blocks is an important goal of nanotechnology, and specifically teaches an antibody-containing aggregate constructed from gold-labeled streptavidin (STV) and a biotinylated IgG. See page 2265, Scheme 1. Neimeyer teaches selecting a biostructure based on its shape (i.e. DNA is a promising material for the fabrication of nanostructured scaffolds) and labeling the DNA with an antibody conjugated to an inorganic particle via streptavidin-biotin interaction, thereby generating a
PNG
media_image1.png
722
534
media_image1.png
Greyscale
biometallic aggregates. See also page 2267, right column, first full paragraph. Neimeyer teaches transmission electron microscopy (TEM) images of antigen coated surfaces showing clear accumulations of clusters in which isolated chain-like structures were evident. See page 2267, right column, first full paragraph and Figure 2B.
With respect to claim 2, Neimeyer teaches as above. Neimeyer teaches labeling based on an antigen-antibody reaction, i.e. DNA-STV hybrid was coupled with a biotinylated antibody against IgG from mice and hybrids were coupled with biotinylated gold clusters. See page 2267, right column and Figure 2B.
With respect to claims 13 and 18, Neimeyer teaches the inorganic particles comprising colloidal gold particles. See page 2267, right column, first full paragraph and Figure 2B.
With respect to claim 17, Neimeyer teaches colloidal goal labels in the form of spherical shape with average particle sizes of 1.3nm - 4.5nm. TEM of gold-labeled aggregates reveal stretched and sharply bent structures (i.e. rod shape,) see Figure 2 and page 2267, left column.
With respect to claim 19, Neimeyer teaches DNA as the biostructures as detailed above.
With respect to claim 20, Neimeyer teaches a structure manufactured as detailed above. See also, page 2265.
Claims 1, 2 and 13, 17-20 are rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by Neimeyer (Nanoparticles, Proteins, and Nucleic Acids: Biotechnology Meets Materials Science. Angew. Chem. Int. Ed. 2001, 40:4128-4158. Herein after Neimeyer 2001.)
With respect to claim 1, in a review article, Neimeyer 2001 discloses bottom-up approach for the engineering of small-scale devices (e.g. sensor or catalysts) using colloidal nanoparticles comprised of metal and semiconductor materials. See page 4129 and page 4131, Fig. 2. Neimeyer 2001 teaches biomolecule-directed nanoparticles organization driven by biospecific interaction where the two particle batches assemble to form extended nanoparticle networks, which in some cases can grow to the size of macroscopic materials. A major motivation for this approach is the unique properties of biomolecular linkers, which promise new applications such as tunable and/or switchable materials. In particular, the tremendous recognition capabilities of biomolecules, and their potential to be addressed and manipulated through biochemical procedures that use designed tools such as enzymes, should provide the basis for entirely novel routes to construct advanced materials rationally. See page 4134, left column. Neimeyer 2001 teaches hapten groups used to cross-link nanoparticles, which are previously coated with antibody molecules that specifically recognize the hapten group (See page 4134, right column and Figure 6). Functionalized gold and silver nanoparticles with IgG and IgE, which had a specificity directed against either the d-biotin or the dinitrophenyl (DNP) group allow the cross-linking of the IgG functionalized nanoparticles. The monospecific linker 8, which is comprised of two DNP moieties, and the bispecific linker 9 were used (page 4135, Figure 6) to induce the directed assembly of homo-oligomeric or heterodimeric aggregates, respectively. The precipitate formed was characterized by transmission electron microscopy (TEM) and large disordered 3D networks of discrete nanoparticles were found.
PNG
media_image1.png
722
534
media_image1.png
Greyscale
Specifically, Neimeyer 2001 teaches selecting the appropriate DNA as biotempate (page 4140) and labeling such template using immunoglobin molecules carrying visualizable labels. Neimeyer 2001 discloses covalent DNA-streptavidin conjugates as building blocks for novel biometallic nanostructures. Neimeyer 2001 discloses generation of nanoscale structural and functional devices by self-assembly of small molecular building blocks is an important goal of nanotechnology, and specifically teaches an antibody-containing aggregate constructed from gold-labeled streptavidin (STV) and a biotinylated IgG. See page 4139, Figure 12. Neimeyer 2001 teaches labeling the DNA with an antibody conjugated to an inorganic particle via streptavidin-biotin interaction, thereby generating a biometallic aggregates. Neimeyer 2001 teaches the functionality of the antibody in the aggregate allows the targeting of the biometallic nanostructures to specific tissues, substrates, or other surfaces. See page 4139, left column.
With respect to claim 2, Neimeyer 2001 teaches labeling based on an antigen-antibody reaction. Neimeyer 2001 teaches the functionality of the antibody in the aggregate allows the targeting of the biometallic nanostructures to specific tissues, substrates, or other surfaces. See page 4139, left column. See also Figure 20, page 4147.
With respect to claims 13 and 18, Neimeyer 2001 teaches the inorganic particles comprising colloidal gold particles. See page 4133, #3. Biomolecule-Directed Nanoparticle Organization, paragraph bridging page 4134.)
With respect to claim 17, Neimeyer 2001 teaches spherical gold nano particles. See page 4132.
With respect to claim 19, Neimeyer 2001 teaches DNA as the biostructures as detailed above.
With respect to claim 20, Neimeyer teaches a structure manufactured as detailed above. See also, page 4143, right column, 4.3 Bio-Nanoreactors.
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.
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.
Claims 14-16 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Neimeyer 2001.
Neimeyer 2001 is discussed above. This reference differs from the instant claims in failing to specifically teach a method for making the catalyst by synthesizing a multi-material particles as a core-shell structure by applying another material to the inorganic particles disposed on the biostructure. However, Neimeyer 2001 gold nanoparticles functionalized with proteins, e.g. antibody molecules adsorbed on colloidal gold allowing the biospecific labeling of
PNG
media_image2.png
758
388
media_image2.png
Greyscale
distinguished regions of tissue samples and subsequent TEM analysis. The visibility of the clusters can be improved by a wet-chemical silver enhancement step resulting in a core-shell structure by applying the silver to an outside of the inorganic particles disposed on the biostructures. See page 4146 and Fig. 20.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to use the method taught by Neimeyer 2001 to make a catalyst comprising labeling a bio-template using colloidal gold conjugated antibody and to cover the resulting biostructure with silver in order to enhance visibility and improve detection limits.
Claims 3 and 6-8 are rejected under 35 U.S.C. 103 as being unpatentable over Neimeyer (Angew. Chem. Int. Ed. 1998. 37, No. 16. PP 2265-2268) in view of Neimeyer 2001 (Angew. Chem. Int. Ed. 2001, 40:4128-4158) and Gouda et al (USP 9970847).
Neimeyer is discussed above. This reference differ from the instant claims in failing to teach labeling the biostructures using secondary antibodies or secondary antibody pairs.
Neimeyer 2001 teaches antibody-pairs are known in the art. Specifically, Au nanoparticles were coupled to a secondary antibody. The latter was used to detect a primary antibody bound through specific immunosorption to the antigen immobilized on a gold sensor surface. The immunosorptive binding of the colloidal gold to the sensor surface led to a large shift in plasmon angle, a broadened plasmon resonance, and an increase in minimum reflectance, thereby allowing picomolar detection of the antigen. Similarly, an improvement in sensitivity by about 1000-fold was obtained in nucleic acid hybridization analysis, when a colloidal gold/oligonucleotide conjugate was used as a probe (Figure 21). See also page 4146, right column.
PNG
media_image3.png
528
658
media_image3.png
Greyscale
PNG
media_image4.png
516
656
media_image4.png
Greyscale
Gouda teaches throughout the publication a method of using labeled probes for staining in order to detect and quantify the expression amount and location of a biological substance within a tissue sample (Abstract and Figures 1-3).
With respect to claims 3 and 6-8, Gouda teaches labeling a biostructure by using a primary antibody; staining the primary antibody by using a secondary antibody conjugated to inorganic particle (See Figures 2 & 3, and col. 14 lines 28-32: an antibody 21 that recognizes a specific biological substance 10 and binds thereto [i.e. a primary antibody], a biotinylated antibody 50-80 that recognizes said antibody and binds thereto [i.e. a secondary antibody], a streptavidinylated peroxidase label 70-31, and, a biotinylated fluorescent label 80-40.) See column 5, lines 41-46. Gouda teaches examples of the phosphor [i.e. the fluorescent label] including fluorescent substances such as organic fluorescent dyes and semiconductor nanoparticles, and fluorescent aggregates in which multiple fluorescent substances are aggregated.
Therefore, it would have been obvious to one of ordinary skill in the art before the effectively date of the instant application to modify the method of Neimeyer and Neimeyer 2001 to make the catalyst by employing the secondary labeling system taught by Neimeyer 2001 and Gouda for the advantage of highly precise staining regardless of the expression amount and/or location of the biological substance in a tissue sample (Gouda, column 2, line 60 through column 2, line 3 and lines 24-27.) A skilled artisan would have had a reasonable expectation of success in modifying the method Neimeyer and Neimeyer 2001 by using the secondary labeling system of Gouda because Neimeyer 2001 and Gouda teach this system is well known in the art, has been widely used and area readily available (Gouda, Col. 14, ln 4-39).
A skilled artisan would have had a reasonable expectation of success in modifying the method Neimeyer or Neimeyer 2001 by using the secondary labeling system of Gouda to make the catalyst because the modification as suggested would have been obvious since it amounts to nothing more than applying a known techniques, i.e. indirect labeling system, to a known method, i.e. specific labeling of biological material, ready for improvement to yield predictable results, i.e. localizing, labeling and aggregating metallic particles to generate biometallic nanostructures, because Neimeyer and Neimeyer 2001 disclose DNA as a bio-template for fabrication of nanostructured scaffolds and for the precise spatial positioning of conducting polymers (Neimeyer, page 2265, first column), and Gouda teaches their system is highly precise staining of biological structures regardless of the expression amount and/or location of the biological substance in a tissue sample (Gouda, column 2, line 60 through column 2, line 3 and lines 24-27.)
Claims 4-5 and 9-12 are rejected under 35 U.S.C. 103 as being unpatentable over Neimeyer et al, Neimeyer 2001, Gouda et al as applied in claims 1 and 6 above and further in view of Atherton et al (Atherton et al., 2001. Multiple Labeling Techniques for Fluorescence Microscopy. In: Brooks, S.A., Schumacher, U. (eds) Metastasis Research Protocols. Methods in Molecular Medicine, vol 57. Humana Press.)
Neimeyer et al, Neimeyer 2001 and Gouda are discussed above. These references differ from the instant claims in failing to teach making a catalyst by labeling different bio-templates using different primary-secondary antibodies system.
Regarding claims 4-5 and 9-12, Atherton teaches simultaneously labeling of multiple antigens within a cell or tissue using antibodies. See Chapter 3, pp. 41, Introduction, par. 1, lines 3-5. Atherton teaches much information can be derived by localizing a single protein/peptide, it is often useful to label simultaneously for two or more antigens within the same cells or tissue sections. Staining primary antibodies with multiple secondary antibodies conjugated to different labels. See page 41, par. 2, lines 3-6 where Atherton teaches indirect immunofluorescence using secondary antibodies conjugated to different fluorochromes. This approach has the advantage that multiple secondary antibodies can bind to each primary antibody.
Therefore, it would have been obvious to one of ordinary skill in the art before the effectively date of the instant application to further modify the method of Neimeyer et al and Neimeyer 2001 as modified by Gouda to make the catalyst by employing multiple structures using different primary antibodies and multiple secondary antibodies conjugated with different labels, as taught by Atherton for the advantage of simultaneously labeling two or more specific biostructures within the same bio-template, i.e. cells or tissue sections and because of the advantage that multiple secondary antibodies can bind to each primary antibody, resulting in an amplification of the signal (Atherton et al., Chapter 3, pp. 41, Introduction, par. 2, lines 5-6).
A skilled artisan would have had a reasonable expectation of success in modifying the methods of Neimeyer or Neimeyer 2001 by labeling multiple biotemplates using multiple primary-secondary antibody labeling systems because Gouda teaches this system is well known in the art, has been widely used and are readily available (Gouda, Col. 14, ln 4-39) and Atherton teaches it is advantageous to simultaneously label more than one antigens at the same time.
Furthermore, the modification as suggested would have been obvious because it amounts to nothing more than applying a known techniques, i.e. indirect labeling system, to a known method, i.e. specific labeling of biological material, ready for improvement to yield predictable results, i.e. localizing, labeling and aggregating metallic particles to generate biometallic nanostructures, because Neimeyer and Neimeyer 2001 disclose DNA as a bio-template for fabrication of nanostructured scaffolds and for the precise spatial positioning of conducting polymers (Neimeyer, page 2265, first column), and Gouda teaches their system is highly precise staining of biological structures regardless of the expression amount and/or location of the biological substance in a tissue sample (Gouda, column 2, line 60 through column 2, line 3 and lines 24-27) and Atherton teaches it is well known in the art to take advantage of the specificities of antibodies to simultaneously label two or more antigens within the same cells or tissue sections.
Response to Arguments
Applicant’s arguments filed January 1, 2025 with respect to claims 1-20 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to /BAO-THUY L NGUYEN/ whose telephone number is (571)272-0824. The examiner can normally be reached M-Th 8:00 am - 4:00 pm (ET); Alternate Friday 9:00 am - 12:00 Noon.
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, Patricia (Tricia) Mallari can be reached at 571.272.4729. 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.
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 August 17, 2025