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 .
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.
Withdrawn Rejections
The rejection of claims 5 and 8 under nonstatutory double patenting is withdrawn in response to the amendments.
Priority
Claims 1, 4-6 and 8 fail to receive foreign priority benefit to application KR10-2019-0025702 filed on 3/6/2019 and to application No. KR10-2020-0027910 filed on 3/5/2020 because the limitation of “a silica particle as a base particle” is not disclosed. Claims 1, 4-6 and 8 have an effective filing date of 03/06/2020, which is the filing date of PCT/KR2020/003145.
Status of the Claims
Claims 1, 4-5 and 8 are pending; claims 1 and 4-5 are amended, claims 2-3, 6-7 and 9 are canceled; no claims are withdrawn. Claims 1, 4-5 and 8 are examined below.
New Rejections
Claim Rejections - 35 USC § 112
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 1, 4-5 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 1 recites “A composition for differentially diagnosing Alzheimer's disease and mild cognitive impairment, comprising a first silver nanogap shell with an antibody specific for amyloid beta (Aβ) 40 introduced and a second silver nanogap shell with an antibody specific for Aβ42 introduced as active ingredients,…”.
However, it is not clear what is meant by the composition comprising “a first silver nanogap shell with an antibody specific for amyloid beta (Aβ) 40 introduced”. The language used, i.e. “introduced” is confusing. A person having ordinary skill in the art would not be capable of recognizing the metes and bounds of the claim.
Claim 1 further recites “and the antibody is introduced on the surface of the metal layer” in line 15. However, it is not clear which antibody is being referred because “the antibody” could be referring to the antibody specific for amyloid beta (Aβ) 40, the antibody specific for Aβ42, or both. Because of this, a person having ordinary skill in the art would not be capable of recognizing the metes and bounds of the claim.
Claim 4 is included with this rejection because it depends from rejected claim 1 but fails to clarify the scope of patent prosecution sought.
Claim 5 recites “A method for diagnosing Alzheimer's disease, comprising:(1) a step of preparing AgNGS-Aβ40 by conjugating an antibody specific for amyloid beta (Aβ) 40 on the surface of a silver nanogap shell (AgNGS); (2) a step of preparing AgNGS-Aβ42 by conjugating an antibody specific for Aβ42 on the surface of AgNGS…”.
However, it is not clear which AgNGS is being referred in step (2) because the claim fails to recite “the AgNGS” or “said AgNGS” and therefore could be referring to a second AgNGS or the AgNGS of step (1). Because of this, a person having ordinary skill in the art would not be capable of recognizing the metes and bounds of the claim.
Claim 8 is included with this rejection because it depends from rejected claim 5 but fails to clarify the scope of patent prosecution sought.
Maintained Rejections
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 5 and 8 are rejected under 35 U.S.C. 101 because the claimed invention is directed to at least one judicial exception without significantly more.
The U.S. Patent and Trademark Office recently revised the MPEP with regard to § 101 (see the MPEP at 2106). Regarding the MPEP at 2106, in determining what concept the claim is “directed to,” we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract ideas (i.e., mathematical concepts, certain methods of organizing human activity such as a fundamental economic practice, or mental processes); and
(2) additional elements that integrate the judicial exception into a practical application (see MPEP § 2106.05(a)-(c), (e)-(h)).
Only if a claim (1) recites a judicial exception and (2) does not integrate that exception into a practical application, do we then look to whether the claim contains an “‘inventive concept’ sufficient to ‘transform’” the claimed judicial exception into a patent-eligible application of the judicial exception. Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82). In so doing, we thus consider whether the claim:
(3) adds a specific limitation beyond the judicial exception that is not “well-understood, routine, conventional” in the field (see MPEP § 2106.05(d)); or
(4) simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception.
See MPEP 2106.
ELIGIBILITY STEP 2A: WHETHER A CLAIM IS DIRECTED TO A JUDICIAL EXCEPTION
Step 2A, Prong 1
Prong One asks does the claim recite an abstract idea, law of nature, or natural phenomenon? In Prong One examiners evaluate whether the claim recites a judicial exception, i.e. whether a law of nature, natural phenomenon, or abstract idea is set forth or described in the claim. While the terms "set forth" and "described" are thus both equated with "recite", their different language is intended to indicate that there are two ways in which an exception can be recited in a claim. For instance, the claims in Diehr, 450 U.S. at 178 n. 2, 179 n.5, 191-92, 209 USPQ at 4-5 (1981), clearly stated a mathematical equation in the repetitively calculating step, and the claims in Mayo, 566 U.S. 66, 75-77, 101 USPQ2d 1961, 1967-68 (2012), clearly stated laws of nature in the wherein clause, such that the claims "set forth" an identifiable judicial exception. Alternatively, the claims in Alice Corp., 573 U.S. at 218, 110 USPQ2d at 1982, described the concept of intermediated settlement without ever explicitly using the words "intermediated" or "settlement." See MPEP 2106.04 (II)(A)(1).
Independent claim 5 recites “[a] method for diagnosing Alzheimer's disease, comprising:…biological sample…(5) a step of diagnosing as Alzheimer's disease when the ratio of Aβ40 and Aβ42 is from 2.5 to 999”.
The natural relationship to which the claims are directed (i.e., the relation between Aβ40 and Aβ42 levels and Alzheimer's disease) is a law of nature. Similar concepts have been held by the courts to constitute law of nature/ natural phenomena, as in the identification of a correlation between the presence of myeloperoxidase in a bodily sample (such as blood or plasma) and cardiovascular disease risk in Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1361, 123 USPQ2d 1081, 1087 (Fed. Cir. 2017). In Mayo, the Supreme Court found that a claim was directed to a natural law, where the claim required administering a drug and determining the levels of a metabolite following administration, where the level of metabolite was indicative of a need to increase or decrease the dosage of the drug. See Mayo Collaborative Services v. Prometheus Labs., Inc., 566 U.S. 66, 74 (2012).
The instant claims are similar to those in Mayo as they involve a "relation itself [which] exists in principle apart from any human action" (id. at 77), namely the relationship between the naturally occurring levels of Aβ40 and Aβ42 in a biological sample and the presence of Alzheimer's disease.
The correlation between Aβ40 and Aβ42 levels and disease is a judicial exception as it exists in principle apart from any human action; the correlation itself therefore cannot form the basis for eligibility. Similarly, it is a naturally occurring phenomenon that Aβ40 and Aβ42 levels are elevated to different extents in Alzheimer's disease compared with other disorders.
Additionally, the claims also recite “(4) a step of calculating the ratio of Aβ40 and Aβ42 by measuring a surface-enhanced Raman scattering (SERS) signal of the complex in the sample”. The claimed step of “calculating the ratio” may also be categorized as abstract ideas, namely mathematical calculations. The claims, under their broadest reasonable interpretation, cover performance of calculating the ratio solely within the human mind, or by a human using pen and paper.
Furthermore, claim 8 merely narrows the biological sample used in the judicial exceptions. Therefore, claim 8 is also directed to at least one judicial exception.
Step 2A, Prong 2
The claims also recite “(1) a step of preparing AgNGS-Aβ40 by conjugating an antibody specific for amyloid beta (Aβ) 40 on the surface of a silver nanogap shell (AgNGS); (2) a step of preparing AgNGS-Aβ42 by conjugating an antibody specific for Aβ42 on the surface of AgNGS; (3) a step of inducing the formation of a silver nanogap shell (AgNGS)-based sandwich complex by mixing the AgNGS-Aβ40 and the AgNGS-Aβ42 with a biological sample in vitro…wherein the silver nanogap shell (AgNGS) comprises: a silica particle as a base particle; and a silver (Ag)-containing metal layer completely surrounding the silica particle and having a surface with a plurality of gaps formed, and wherein a Raman label is inserted into the plurality of gaps”. However, such steps of preparing and mixing the reagents are insufficient to integrate the judicial exception(s) because the purpose is merely to obtain data. This does not go beyond insignificant presolution activity, i.e., a mere data gathering step necessary to use the correlation, similar to the fact pattern in In re Grams, 888 F.2d 835 (Fed. Cir. 1989) and Ariosa Diagnostics, Inc. v. Sequenom, Inc. (Fed. Cir. 2015).
ELIGIBILITY STEP 2B: WHETHER THE ADDITIONAL ELEMENTS CONTRIBUTE AN "INVENTIVE CONCEPT"
Although the claims recite antibodies that specifically bind to Aβ40 and Aβ42, no particular or specific antibody is set forth. Furthermore, in this case, it was well-understood, routine and conventional to use AgNGS for detection.
For example, Kim et al. (KR 101944346 B1)-Cite No. e of IDS 9/7/2021(“Kim”) teaches a composition comprising a silver nanogap shell, wherein the silver nanogap shell comprises: a silica particle as a base particle; and a silver (Ag)-containing metal layer completely surrounding the silica particle (Abstract, page 7 para. 4) and having a surface with a plurality of gaps formed, and wherein a Raman label is inserted into the plurality of gaps (page 9 last paragraph and page 10 paragraph 1) to enable surface-enhanced Raman scattering (SERS) detection with a sensitivity of below 1 pg/ml (page 7 para. 2).
Also, Kim et al. (US 11287385 B2) (“Lee”) teaches the composition comprising a silver nanogap shell, wherein the silver nanogap shell comprises: a silica particle as a base particle; and a silver (Ag)-containing metal layer (claims 1 and 4) comprising: an inner surface completely surrounding and in contact with the silica particle; and an outer surface with a plurality of gaps disposed on the outer surface, and wherein a Raman label is inserted into the plurality of gaps (claims 1 and 3) to enable surface-enhanced Raman scattering (SERS) detection with a sensitivity of below 1 pg/ml.
See also Long et al. (CN 105562714 A) (“Long”). Long also teaches a AgNGS for sensitive SERS detection of analytes (“The invention claims a nanometre material for SERS detection and preparation method thereof, wherein the nano-material outside the shell of core composed of an inner core and a coating, the kernel whose grain diameter is 300 ~ 450 nanometer porous silicon dioxide particles. the shell is composed of particle diameter is 5 ~ 80 nanometer silver nanoparticle aggregate is formed; the preparation method comprises the following steps: preparing porous silicon dioxide particles and preparing porous silicon dioxide-silver shell nano-material, it is obtained by preparing kernel of the nanometer material whose grain diameter is 300 ~ 450 nanometer porous silicon dioxide particles. the abundant micro-micro-hole silicon dioxide particle surface can load more Raman label molecules, so under the action of the external laser, the Raman marker molecules in the outer layer of the silver nanoparticles produced by the local surface electromagnetic field for generating a very high intensity of the SERS signal is output such that the nanometre material has higher SERS activity, so as to greatly improve the SERS detection capability” Abstract).
Furthermore, conjugating generic antibodies for amyloid beta 40 or 42 to the surface of silver particles and mixing these with a serum sample is also well-understood, routine and conventional.
For example, see Hu et al. Sensors and Actuators B 234 (2016) 63–69 http://dx.doi.org/10.1016/j.snb.2016.04.159 (“Hu”). Hu suggest conjugating an antibody specific for amyloid beta on the surface of silver particles (Scheme 1, page 64) and a step of inducing the formation of a silver particle based sandwich complex by mixing the silver particles with a biological sample in vitro, wherein the biological sample is one or more noninvasive sample selected from the group consisting of blood and serum (Scheme 1 page 64, page 65 col. 2 para. 2, page 67 col. 2 para. 3).
The courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity:
i. Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017).
When recited at this high level of generality, there is no meaningful limitation, such as a particular or unconventional machine or a transformation of a particular article, in steps (1)-(3) of claim 5 that distinguishes it from well-understood, routine, and conventional data gathering activity engaged in by scientists prior to applicant’s invention, and at the time the application was filed.
For all of these reasons, the claims fail to include additional elements that are sufficient to amount to significantly more than the judicial exception(s).
Maintained Rejections
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.
Claims 1, 4-5 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (KR 101944346 B1)-Cite No. e of IDS 9/7/2021 in view of Hu et al. Sensors and Actuators B 234 (2016) 63–69 http://dx.doi.org/10.1016/j.snb.2016.04.159 and Chiu et al. Current Alzheimer Research Volume 9, Issue 10, pages 1142-1148, Published 2012 (Cite No. U of PTO 892 9/6/2024) The Kim reference is also being cited on a PTO 892 form and a copy is being provided because the copy provided by Applicant is in a foreign language.
Regrading claim 1, although the claim is indefinite (see 112b rejection above), in the interest of compact prosecution, the claim is interpreted as reciting “comprising a first silver nanogap shell with an antibody specific for amyloid beta (Aβ)40 specific for amyloid beta (Aβ)40 and the antibody specific for Aβ42 are introduced on the surface of the metal layer”.
Kim suggests a composition for differentially diagnosing Alzheimer’s disease and mild cognitive impairment, comprising a first and second silver nanogap shell, wherein the silver nanogap shell comprises: a silica particle as a base particle; and a silver (Ag)-containing metal layer completely surrounding the silica particle (“[a] composite particle is provided. The composite particle comprises: a base particle; a metal layer surrounding the base particle and having a surface on which a plurality of gaps are formed; and a marker provided on the metal layer, and provided in the gaps of the metal layer” Abstract, “The singular forms "a", "an", and "the" include plural referents” page 3 para. 2, “composite particle was prepared by the method according to Example 1 described above, in which a silver layer was formed on silica particles, and then a Raman label was formed on the silver layer” page 7 para. 4). Note “for differentially diagnosing Alzheimer’s disease and mild cognitive impairment” are drawn to the intended use of the claimed composition. Therefore, these are not considered limiting the composition. Kim further suggests having a surface with a plurality of gaps formed, and wherein a Raman label is inserted into the plurality of gaps (“according to Example 1, the Raman markers are provided in a plurality of gaps formed on the surface of the silver layer so that the Raman markers are stably bonded to the silver layer” page 9 last paragraph and page 10 paragraph 1, see Figure 3 and showing that the “120: Marker” (page 10) is disposed in the gaps).
Kim fails to teach the first silver nanogap shell with an antibody specific for amyloid beta (Aβ)40 and the second silver nanogap shell with an antibody specific for Aβ42 introduced as active ingredients and wherein the antibody is introduced on the surface of the metal layer.
Hu teaches “a colorimetric immunosensor using antibody modified-silver nanoparticles (AgNPs) for the specific detection of Aβ(1–40/1–42), which is now can be viewed as a predictor for preclinical diagnosis of Alzheimer’s disease” (Abstract). Hu teaches a composition for diagnosing Alzheimer's disease with an antibody specific for amyloid beta as an active ingredient, comprising a particle and a silver (Ag)-containing metal surface and the antibody introduced on the surface of the metal (see Scheme 1 showing the antibodies introduced on the surface of the silver nanoparticle, page 64). Hu further teaches that “Alzheimer’s disease (AD) is the most common cause of dementia, associated with progressive loss of cognitive function and behavioral abilities in the elderly population. β-Amyloid (Aβ), which mainly composes of Aβ1–40 and A β1–42 species…is prone to assembling into soluble oligomers that have been proposed to be the culprit of cognitive decline in AD…years or decades before the onset of AD” (page 63 col. 1 para. 1).
Chiu teaches a composition for diagnosing Alzheimer’s disease and for differentially diagnosing Alzheimer's disease and mild cognitive impairment (“New Assay for Old Markers-Plasma Beta Amyloid of Mild Cognitive Impairment and Alzheimer's Disease” Title, see Table 1 and Figure 1, “immunomagnetic reduction assay (IMR) to determine the plasma levels of Aβ… plasma Aβ1-42 is a useful biomarker for AD. The Aβ1-42/Aβ1-40 ratio improves the diagnostic power of the plasma Aβ biomarkers” Abstract, “Our study showed that the Aβ1-42/Aβ1-40 ratio can be used to differentiate between control, MCI, and AD subjects” page 1146 col. 2 para. 1) comprising a first particle with an antibody specific for amyloid beta (Aβ) 40 and a second particle with an antibody specific for Aβ42 introduced as an active ingredients (“bind the antibodies (anti-Aβ1-40 (sc53822, Santa Cruz Biotech) and anti-Aβl-42 (437900, Invitrogen)) to the dextran of the magnetic nanoparticles” page 1144 col. 2 para. 2). Note that although Chiu teaches both first and second particles with both Aβ40 and Aβ42 antibodies, the claim is not limited to the exclusion of other antibodies in the particle as noted by the language “comprising” used in line 2. Therefore, the particles taught by Chiu are reasonably interpreted as being a first particle with an antibody specific for amyloid beta (Aβ) 40 and a second particle with an antibody specific for Aβ42. Chiu further suggests that differentially diagnosing AD and mild cognitive decline enables clinical staging of the disease (“Furthermore, the Aβ1-42/Aβ1-40 ratio can improve the diagnosis because we can formulate useful cut-off values to differentiate between control, MCI and AD subjects. This ratio is significant in clinical staging and APOE ɛ4 load. Higher Aβ1-42/Aβ1-40 ratios were found in patients with higher clinical staging and in those carrying the APOE ɛ4 allele” page 1147 col. 1 last paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Kim to include an antibody specific for amyloid beta as an active ingredient introduced on the surface of the first and second silver particles taught by Hu because Hu teaches that amyloid beta is "the culprit of cognitive decline in AD…years or decades before the onset of AD" (Abstract) and teaches that "Alzheimer’s disease (AD) is the most common cause of dementia…in the elderly" (Abstract). Therefore, one would have been motivated to make such a modification in order to diagnose AD early in the elderly population, which as suggested by Hu, is a current need in the field. A person having ordinary skill in the art would have had a reasonable expectation of success because Kim and Hu are both drawn to particles comprising a surface made of silver for biotechnology applications.
It would have been further prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Kim in view of Hu to rely on the first particle having an antibody being specific for amyloid beta (Aβ) 40 and the second particle having an antibody specific for Aβ42 taught by Chiu because Chiu teaches that Aβ1-42 is a useful biomarker of AD and Aβ1-42/Aβ1-40 ratio improves the diagnostic power, and Kim in view of Hu is concerned with diagnosing AD, which is a current need in the field. Also, Chiu suggests that differentiating between AD and MCI is useful for clinical staging of the disease. Therefore, a person having ordinary skill in the art would have found it obvious to use antibodies specific for Aβ40 and Aβ42 and differentially diagnose AD and MCI, namely because relying on these specific antibodies improves the diagnostic power and differentially diagnosing is useful in staging the disease, a current need in the field. A person having ordinary skill in the art would have had a reasonable expectation of success given that both Kim in view of Hu and Chiu are drawn to compositions comprising particles for diagnosing Alzheimer’s disease.
Regarding claim 4, Kim in view of Hu and Chiu teach the composition for differentially diagnosing Alzheimer's disease and mild cognitive impairment according to claim 1 as discussed above.
Hu further suggest wherein the antibodies of the first and second silver nanogap shells (AgNGSs) each form a AgSNGs-based sandwich complex by mixing with one or more noninvasive biological sample selected from the group consisting of blood and serum (see Scheme 1 showing the sandwich complex page 64, “serum samples” page 65 col. 2 para. 2, “to quantitatively detect Aβ(1–40/1–42) in real blood samples” page 67 col. 2 para. 3 of Hu).
Chiu further teaches that “[a] lumbar puncture to collect CSF is an invasive treatment
with potential side effects… a blood sample is considered the gold standard and is easily obtained in clinical settings” (page 1142 col. 2 para. 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Kim in view of Hu and Chiu to rely on the wherein the antibodies of the first and second AgNGSs each form a silver nanogap shell (AgNGS)-based sandwich complex by mixing with one or more noninvasive biological sample selected from the group consisting of blood and serum taught by Hu because Chiu teaches that blood is the gold standard sample type in the context of diagnostic assays, and is safer and easier to get than CSF. A person having ordinary skill in the art would have had a reasonable expectation of success given that Kim, Hu and Chiu all teach particles for biotechnological applications.
Regarding claims 5 and 8, although claim 5 is indefinite (see 112b rejection above), in the interest of compact prosecution, the claim is interpreted as reciting “(2) a step of preparing AgNGS-Aβ42 by conjugating an antibody specific for Aβ42 on the surface of the AgNGS”.
Kim suggests a method of detecting a target substance (“More particularly, the present invention relates to a composite particle… areas such as… Biotechnology… developed to improve the sensitivity and reliability of the sensor… For example, Korean Patent Registration No. 10-1565652 discloses a biosensor having an excellent sensitivity and selectivity for a target substance” page 2 paras. 2-5) comprising a step of preparing AgNGS wherein the silver nanogap shell (AgNGS) comprises: a silica particle as a base particle; and a silver (Ag)-containing metal layer completely surrounding the silica particle and having a surface with a plurality of gaps formed, and wherein a Raman label is inserted into the plurality of gaps (“The composite particles according to the examples of the present invention were prepared” page 6 para. 6, page 9 last paragraph and page 10 paragraph 1, see Figure 3 showing that the “120: Marker” (page 10) is disposed in the gaps, see also Figs. 1-7); and a step of measuring a SERS signal of a complex of the AgNGS and the target substance (“FIG. 13 is a photograph showing a comparison of the SERS signal intensities of the composite particles according to Example 1 and Comparative Example 1 of the present invention” page 9 para. 4) .
Kim fails to teach diagnosing Alzheimer’s disease, conjugating an antibody specific for amyloid beta (Aβ) 40 and an antibody specific for Aβ42 on the surface of the AgNGS; (3) a step of inducing the formation of a silver nanogap shell (AgNGS)-based sandwich complex by mixing the AgNGS-Aβ40 and the AgNGS-Aβ42 with a biological sample in vitro, wherein the biological sample is one or more noninvasive sample selected from the group consisting of blood and serum; (4) a step of calculating the ratio of Aβ40 and Aβ42; and (5) a step of diagnosing as Alzheimer's disease when the ratio of Aβ40 and Aβ42 is from 2.5 to 999.
Hu suggest a method for diagnosing Alzheimer's disease (“diagnosis of Alzheimer’s disease” Abstract) comprising conjugating an antibody specific for amyloid beta on the surface of silver particles (see Scheme 1 showing the antibodies introduced on the surface of the silver nanoparticle, page 64), a step of inducing the formation of a silver particle based sandwich complex by mixing the silver particles with a biological sample in vitro, wherein the biological sample is one or more noninvasive sample selected from the group consisting of blood and serum (Scheme 1 page 64, page 65 col. 2 para. 2, page 67 col. 2 para. 3), and (4) a step of calculating the ratio of Aβ40 and Aβ42 by measuring a signal of the complex in the sample (“an increasing number of investigators suggest that both the ratio of Aβ1–40 to Aβ1–42 and the total amount of the two types can be regarded as better predictors than single indicator” page 63 col. 2 para. 1). Hu further teaches that “Alzheimer’s disease (AD) is the most common cause of dementia, associated with progressive loss of cognitive function and behavioral abilities in the elderly population. β-Amyloid (Aβ), which mainly composes of Aβ1–40 and A β1–42 species…is prone to assembling into soluble oligomers that have been proposed to be the culprit of cognitive decline in AD…years or decades before the onset of AD” (page 63 col. 1 para. 1).
Chiu teaches a method for diagnosing Alzheimer's disease (“New Assay for Old Markers-Plasma Beta Amyloid of Mild Cognitive Impairment and Alzheimer's Disease” Title) comprising conjugating an antibody specific for amyloid beta (Aβ) 40 and an antibody specific for Aβ42 on the surface of particles (page 1144 col. 2 para. 2); (4) a step of calculating the ratio of Aβ40 and Aβ42 by measuring a signal of the complex in the sample; and (5) a step of diagnosing as Alzheimer's disease when the ratio of Aβ40 and Aβ42 is from 2.5 to 999 (“We also obtained a cut-off value of 0.303 for Aβ1-42/Aβl-40 ratios with 85.3% sensitivity and 96.2% specificity” Abstract see Table 1 last row and Fig. 1C). Although Chiu fails to explicitly teach the ratio of Aβ40 to Aβ42, a person having ordinary skill in the art would have recognized that the ratios presented by Chiu are equivalent and within the range of the ratios claimed in the instant application. Chiu teaches in the Abstract a cutoff ratio of 0.303. Therefore, the equivalent Aβ40 to Aβ42 ratio of 0.303 is 0.303-1 = 3.3, which is from 2.5 to 999. Chiu further teaches that “[t]he Aβ1-42/Aβ1-40 ratio improves the diagnostic power of the plasma Aβ biomarkers” (Abstract). Chiu further teaches that “the Aβ1-42/Aβ1-40 ratio can be used to differentiate between control, MCI, and AD subjects” (page 1146 col. 2 para. 1). Chiu further suggests that differentially diagnosing AD and mild cognitive decline enables clinical staging of the disease (“Furthermore, the Aβ1-42/Aβ1-40 ratio can improve the diagnosis because we can formulate useful cut-off values to differentiate between control, MCI and AD subjects. This ratio is significant in clinical staging and APOE ɛ4 load. Higher Aβ1-42/Aβ1-40 ratios were found in patients with higher clinical staging and in those carrying the APOE ɛ4 allele” page 1147 col. 1 last paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Kim to use the AgNGS for diagnosing Alzheimer’s disease comprising a step of conjugating antibodies specific for amyloid beta on the surface of the AgNGS, a step of inducing the formation of a AgNGS-based sandwich complex in a blood serum sample and a step of calculating the ratio of Aβ40 and Aβ42 taught by Hu using a SERS signal of the complex in the sample because Hu suggests that the ratio is a useful parameter in the diagnosis of AD, which is the most common cause of dementia in the elderly population. Therefore, a person having ordinary skill in the art would have been motivated to make such a modification in order to help the elderly population. A person having ordinary skill in the art would have had a reasonable expectation of success because Hu suggests that the ratio of Aβ40 and Aβ42 is well known in the field, furthermore, both Kim and Hu teach the use of a particle with a surface made of silver for use as a biosensor in the field of biotechnology.
It would have been further prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Kim in view of Hu to rely on the step of diagnosing as Alzheimer's disease when the ratio of Aβ40 and Aβ42 is from 2.5 to 999 taught by Chiu because Chiu suggests that this is an effective way of diagnosing AD and the ratio improves the diagnostic power. A person having ordinary skill in the art would have had a reasonable expectation of success because Hu suggests that the ratio of Aβ40 and Aβ42 is well known in the field, furthermore, both Kim in view of Hu and Chiu are drawn to the use of a particle with conjugated antibodies specific for a target substance for use as a biosensor in the field of biotechnology.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1 and 4 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. US 11287385 B2 in view of Kim, Hu and Chiu.
Regarding claim 1 , U.S. Patent No. US 11287385 B2 recites a composition for differentially diagnosing Alzheimer’s disease and mild cognitive impairment, comprising a first silver nanogap shell, wherein the silver nanogap shell comprises: a silica particle as a base particle; and a silver (Ag)-containing metal layer completely surrounding the silica particle (“ A composite particle comprising: a base particle; a metal layer enclosing the base particle and having a surface on which a plurality of gaps are formed” claim 1, “ wherein the base particle comprises a silica particle” claim 4). Note that “for differentially diagnosing Alzheimer’s disease and mild cognitive impairment” are drawn to the intended use of the claimed composition. Therefore, these are not considered limiting the composition. U.S. Patent No. US 11287385 B2 further recites the silica particle having a plurality of gaps formed, and wherein a Raman label is inserted into the plurality of gaps (“wherein the surface of the metal layer has a plurality of convex portions, wherein the gaps are located between the convex portions of the metal layer, and wherein the gaps have sidewall surfaces and a bottom surface; and a marker provided on the metal layer and provided within the plurality of gaps of the metal layer, wherein the marker is provided on the bottom surface of the gaps; wherein the metal layer and the marker are formed from a Ag thiolate polymer provided on a surface of the base particle” claim 1, “wherein the marker comprises a Raman marker” claim 3)
U.S. Patent No. US 11287385 B2 fails to recite the first silver nanogap shell with an antibody specific for amyloid beta (Aβ)40 and a second silver nanogap shell with an antibody specific for Aβ42 introduced as an active ingredients, and the antibody is introduced on the surface of the metal layer.
Kim suggests a composition for detecting a target substance comprising a first and second silver nanogap shell, wherein the silver nanogap shell comprises: a silica particle as a base particle; and a silver (Ag)-containing metal layer completely surrounding the silica particle (Abstract, page 3 para. 2 and page 7 para. 4). Kim further suggests the particles having a surface with a plurality of gaps formed, and wherein a Raman label is inserted into the plurality of gaps (page 9 last paragraph and page 10 paragraph 1, see Figure 3 and showing that the “120: Marker” (page 10) is disposed in the gaps). Kim further suggests that the first and second silver nanogap shells enable the sensing of biological agents with increased sensitivity (“Accordingly, the amount of the markers 120 binding to the metal layer 110 increases, and the reliability and sensitivity of the composite particles 130 can be improved” page 5 para. 6).
Hu teaches “a colorimetric immunosensor using antibody modified-silver nanoparticles (AgNPs) for the specific detection of Aβ(1–40/1–42), which is now can be viewed as a predictor for preclinical diagnosis of Alzheimer’s disease” (Abstract). Hu teaches a composition for diagnosing Alzheimer's disease with an antibody specific for amyloid beta as an active ingredient, comprising a first particle with a silver (Ag)-containing metal surface and the antibody introduced on the surface of the metal (page 64). Hu further teaches the composition further comprising a second particle with a silver (Ag)-containing metal surface and the antibody introduced on the surface of the metal (see Scheme 1 showing the antibodies introduced on the surface of the silver nanoparticles). Hu further teaches that “Alzheimer’s disease (AD) is the most common cause of dementia, associated with progressive loss of cognitive function and behavioral abilities in the elderly population. β-Amyloid (Aβ), which mainly composes of Aβ1–40 and A β1–42 species…is prone to assembling into soluble oligomers that have been proposed to be the culprit of cognitive decline in AD…years or decades before the onset of AD” (page 63 col. 1 para. 1).
Chiu teaches a composition for differentially diagnosing Alzheimer's disease and mild cognitive impairment (Title, Table 1 and Figure 1, Abstract, page 1146 col. 2 para. 1) comprising a first particle with an antibody specific for amyloid beta (Aβ) 40 and a second particle with an antibody specific for Aβ42 introduced as an active ingredient (page 1144 col. 2 para. 2). Chiu further suggests that differentially diagnosing AD and mild cognitive decline enables clinical staging of the disease (page 1147 col. 1 last paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of U.S. Patent No. US 11287385 B2 to include the second silver nanogap shell taught by Kim because Kim suggests that this enables the detection of biological target substances with increased sensitivity and U.S. Patent No. US 11287385 B2 is interested in composite particles with Raman markers. Therefore, one would have been motivated to make such a modification in order to apply a known technique to a known base silver nanogap shell silica particle. A person having ordinary skill in the art would have had a reasonable expectation of success because U.S. Patent No. US 11287385 B2 and Kim are both drawn to silver nanogap shell silica particles with Raman markers inserted into the plurality of the gaps.
It would have been further prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of U.S. Patent No. US 11287385 B2 in view of Kim to include an antibody specific for amyloid beta as an active ingredient introduced on the surface of the silver taught by Hu because Hu teaches that amyloid beta is "the culprit of cognitive decline in AD…years or decades before the onset of AD" (Abstract) and teaches that "Alzheimer’s disease (AD) is the most common cause of dementia…in the elderly" (Abstract). Therefore, one would have been motivated to make such a modification in order to diagnose AD early in the elderly population, which as suggested by Hu, is a current need in the field. A person having ordinary skill in the art would have had a reasonable expectation of success because U.S. Patent No. US 11287385 B2 and Hu are both drawn to particles comprising a surface made of silver.
It would have been further prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of U.S. Patent No. US 11287385 B2 in view of Kim and Hu to rely on the antibody being one or more antibody selected from the group consisting of an antibody specific for amyloid beta (Aβ) 40 and antibody specific for Aβ42 taught by Chiu because Chiu teaches that Aβ1-42 is a useful biomarker of AD and Aβ1-42/Aβ1-40 ratio improves the diagnostic power, and U.S. Patent No. US 11287385 B2 in view of Kim and Hu is concerned with diagnosing AD, which is a current need in the field. Also, Chiu suggests that differentiating between AD and MCI is useful for clinical staging of the disease. Therefore, a person having ordinary skill in the art would have found it obvious to use antibodies specific for Aβ40 and Aβ42 and differentially diagnose AD and MCI, namely because relying on these specific antibodies improves the diagnostic power and differentially diagnosing is useful in staging the disease, a current need in the field. A person having ordinary skill in the art would have had a reasonable expectation of success given that both U.S. Patent No. US 11287385 B2 in view of Kim and Hu and Chiu are drawn to compositions comprising particles for diagnosing Alzheimer’s disease.
Regarding claim 4, U.S. Patent No. US 11287385 B2 in view of Kim, Hu and Chiu address the composition for differentially diagnosing Alzheimer's disease and mild cognitive impairment according to claim 1 as discussed above.
Hu further suggest wherein the antibodies of the first and second silver nanogap shells each form a silver nanogap shell (AgNGS)-based sandwich complex by mixing with one or more noninvasive biological sample selected from the group consisting of blood and serum (Scheme 1 page 64, page 65 col. 2 para. 2, page 67 col. 2 para. 3).
Chiu further teaches that “[a] lumbar puncture to collect CSF is an invasive treatment
with potential side effects… a blood sample is considered the gold standard and is easily obtained in clinical settings” (page 1142 col. 2 para. 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of U.S. Patent No. US 11287385 B2 in view of Kim, Hu and Chiu to rely on the wherein the antibodies of the first and second silver nanogap shells each form a silver nanogap shell (AgNGS)-based sandwich complex by mixing with one or more noninvasive biological sample selected from the group consisting of blood and serum taught by Hu because Chiu teaches that blood is the gold standard sample type in the context of diagnostic assays, and is safer and easier to get than CSF. A person having ordinary skill in the art would have had a reasonable expectation of success given that U.S. Patent No. US 11287385 B2, Kim, Hu and Chiu all teach particles.
Response to Arguments
Applicant's arguments filed 4/27/2026 have been fully considered but they are not persuasive.
Regarding the 101 rejection,
Applicant argues that “The amendment to Claim 5 specifying "surface-enhanced Raman scattering (SERS) signal" measurement, combined with the structural requirement of AgNGS comprising a silica base particle with Ag metal layer having nanogaps, constitutes a practical application that integrates the judicial exception into a specific technological process” (page 5 para. 1).
However, these limitation fail to integrate the judicial exceptions into a practical application because they fail to use, rely on or apply the judicial exception(s) such to amount to a practical application thereof (see rejection above).
Applicant further argues that “The Office Action's evidence of conventionality (Kim, Lee, Long) relates only to general SERS detection of single analytes. None of these references demonstrates that multiplexed SERS-based differential diagnosis using two types of AgNGS in a single composition was well-understood, routine, or conventional as of the effective filing date. Therefore, claim 5 recites significantly more than the alleged judicial exception” (page 5 para. 2).
However, claim 5 fails to recite “multiplexed SERS-based differential diagnosis using two types of AgNGS in a single composition”. The additional limitations of the claims are drawn to a step of preparing AgNGS-Aβ40 by conjugating a generic antibody specific for amyloid beta 40 on the surface of a generic AgNGS, a step of preparing AgNGS-Aβ42 by conjugating a generic antibody specific for amyloid beta 40 on the surface of the generic AgNGS and a step of mixing the AgNGS-Aβ40 and AgNGS-Aβ42 with a sample. These limitations fail to add significantly more than the judicial exceptions because Kim, Lee and Long already demonstrates that SERS-based detection of target analytes with the AgNGSs is well-understood routine and conventional. Furthermore, conjugating generic antibodies for amyloid beta 40 or 42 to the surface of silver particles and mixing these with a serum sample is also well-understood, routine and conventional (see rejection above). All the additional limitations of the claims fail to add significantly more.
Regarding the 103 rejections,
Applicant further argues that “However, Kim does not teach or suggest: (i) combining two differently-functionalized AgNGS particles (one bearing anti-Aβ40 antibody and the other bearing anti-Aβ42 antibody) into a single composition; (ii) using such a two-component composition for multiplexed detection; or (iii) using the ratio of the two detection signals for differential diagnosis of AD and MCI…In contrast, claim 1, as amended, defines an integrated composition for precise ratio calculation of Aβ40/Aβ42, which is a fundamentally different concept from Kim's single-analyte detection probe. Therefore, Applicant respectfully submits that Kim fails to disclose or suggest every claimed feature, and Hu, Chiu, and Yang fail to cure the deficiencies of Kim” (page 6 last paragraph and page 7 paras. 1-2).
However, contrary to Applicant’s remark, Kim in view of Hu and Chiu address (i) combining two differently-functionalized AgNGS particles (one bearing anti-Aβ40 antibody and the other bearing anti-Aβ42 antibody) into a single composition; (ii) using such a two-component composition for multiplexed detection; or (iii) using the ratio of the two detection signals for differential diagnosis of AD and MCI (see rejection above).
Applicant further argues that “Hu uses a colorimetric immunosensor based on surface plasmon resonance (SPR) changes caused by aggregation of silver nanoparticles, measured by UV-Vis spectroscopy. In contrast, the claimed invention uses electromagnetic field enhancement within nanogaps of AgNGS to generate SERS signals, requiring a laser source and Raman spectrometer. …A person of ordinary skill in the art would have had no motivation to apply Hu's colorimetric antibody configuration to Kim's SERS-based AgNGS, as the two systems operate on fundamentally incompatible physical principles” (page 7 paras 3 and 6-7 and page 8 paras. 1-2).
However, the proposed modification of Kim in view of Hu is to conjugate antibodies onto the silver surface of the particles, to mix the particles with a serum sample and calculating the ratio of Aβ40 and Aβ42 for diagnosing Alzheimer’s disease (see rejection above), not to apply the colorimetric based SPR detection method of Hu to Kim’s SERS-based AgNGS as Applicant argues.
Applicant further argues that “Chiu uses immunomagnetic reduction (IMR) using magnetic nanoparticles, where detection is based on measuring changes in the rotational dynamics of magnetic particles via a magnetometer (SQUID-based ac magnetic susceptometer). This is an entirely different measurement modality from SERS-based optical detection. A person of ordinary skill in the art would have had no reason to combine Chiu's IMR-based ratio concept with Kim's SERS-based AgNGS” (page 8 para. 3).
However, the proposed modification of Kim in view of Hu is to conjugate an antibody specific for Aβ40 and an antibody specific for Aβ42 onto the particles as well as diagnosing Alzheimer’s disease when the ratio of Aβ40 and Aβ42 is from 2.5 to 999 (see rejection above), not to combine Chiu's IMR-based ratio concept with Kim's SERS-based AgNGS.
Applicant further argues that “the claimed composition achieves results that are Unexpected…The claimed AgNGS-based composition achieves a limit of detection (LOD) of below 1 pg/ml” (page 8 last paragraph and page 9 para. 1).
However, this argument is not persuasive given that Applicants deleted the limitation regarding the limit of detection below 1 pg/ml. Applicants are arguing an unclaimed limitation.
Applicant further argues that “Channels (a) and (c) correspond to Aβ40 detection, while channels (b) and (d) correspond to Aβ42, and neither interferes with the other. This interference-free multiplexed performance in a complex biological matrix (human serum) is not taught or suggested by Kim, Hu, Chiu, and Yang. Kim demonstrates only single-analyte detection; Hu and Chiu do not use SERS at all” (page 9 para. 2).
However, the claims fail to recite “Channels (a) and (c) correspond to Aβ40 detection, while channels (b) and (d) correspond to Aβ42, and neither interferes with the other”. The claims recite “(4) a step of calculating the ratio of Aβ40 and Aβ42 by measuring a surface-enhanced Raman scattering (SERS) signal of the complex in the sample”. This limitations is addressed by Kim in view of Hu and Chiu (see rejection above). The obviousness analysis above includes a motivation and a reasonable expectation of success.
Applicant further argues that “The claimed composition enables single-tube, simultaneous measurement of both biomarkers under identical experimental conditions. This is not a simple aggregation of two separate detection steps. When Aβ40 and Aβ42 are measured sequentially in separate experiments (as would result from applying Kim's single-analyte approach twice), interexperimental variability (temperature, reagent concentration, operator skill, sample degradation) accumulates and degrades the accuracy of the calculated ratio. The claimed composition eliminates this variability by producing internally normalized results within a single reaction vessel” (page 9 para. 3).
However, the claim is not limited to two separate detection steps. The claims recite “(4) a step of calculating the ratio of Aβ40 and Aβ42 by measuring a surface-enhanced Raman scattering (SERS) signal of the complex in the sample”. Accordingly, Kim in view of Hu and Chiu address the claim. Therefore, these arguments are not persuasive.
Regarding the double patenting rejections,
Applicant further argues that “claim 1 has been amended as noted above. Thus, such nonstatutory double patenting rejection has become moot. Withdrawal of such statutory double patenting rejection is respectfully requested. Further, an e-Terminal Disclaimer has been concurrently filed” (page 10 para. 5).
However, the amendments fail to overcome the double patenting rejection of claims 1 and 4 (see rejection above). Furthermore, although Applicant remarks that “an e-Terminal Disclaimer has been concurrently filed”, no such Terminal Disclaimer has been found by the examiner. Accordingly, the rejection is maintained.
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 FERNANDO IVICH whose telephone number is (703)756-5386. The examiner can normally be reached M-F 9:30-6:00 (E.T.).
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, Gregory S. Emch can be reached at (571) 272-8149. 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.
/Fernando Ivich/Examiner, Art Unit 1678
/CHRISTOPHER L CHIN/Primary Examiner, Art Unit 1677
Prosecution Insights