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
The present application was filed on March 17, 2023. This application claims benefit of U.S. Provisional Patent Application 63/269,595 filed on March 18, 2022.
The effective filing date for claims 1-10 and 12-20 of this application is March 18, 2022. Claim 11 introduces subject matter not supported by the original provisional application. Claim 11 is directed to a method for quantifying a charge variant within an analyte comprising the use of a sample buffer that includes hydroxyl propyl methyl cellulose. This method is not disclosed in the provisional application as originally filed. Thus, the effective filing date for claim 11 of this application is March 17, 2023.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Applicant is reminded of the following requirement:
To claim the benefit of a prior-filed application, a continuation or divisional application (other than a continued prosecution application filed under 37 CFR 1.53(d)), must include a specific reference to the prior-filed application in compliance with 37 CFR 1.78. If the application was filed before September 16, 2012, the specific reference must be included in the first sentence(s) of the specification following the title or in an application data sheet; if the application was filed on or after September 16, 2012, the specific reference must be included in an application data sheet. For benefit claims under 35 U.S.C. 120, 121, 365(c), or 386(c), the reference must include the relationship (i.e., continuation, divisional, or continuation-in-part) of the applications. The presentation of a benefit claim may result in an additional fee under 37 CFR 1.17(w)(1) or (2) being required, if the earliest filing date for which benefit is claimed under 35 U.S.C. 120, 121, 365(c), or 386(c) and § 1.78(d) in the application is more than six years before the actual filing date of the application.
Status of Claims
Claims 1-20 are pending and examined.
Information Disclosure Statement
Two Information Disclosure Statements (IDS), filed 17 March 2023 and 18 July 2023, are acknowledged and have been considered.
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 1-8, 11-13 and 20 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1, line 3, the recitation of “the sample buffer” lacks antecedent support. No sample buffers have been previously recited thus a reference to an unknown sample buffer is indefinite because it is unclear what this sample buffer is.
Claims 1, 2 and 20 are confusing with respect to the recitation of “incubating the capillary in a detection antibody” or “incubating the capillary in a reporter molecule” because it is unclear if the entire capillary is incubated in a detection antibody solution or if detection antibody is introduced into the capillary and the separated variants are incubated with the detection antibody. The specification at paragraph [0094], for example, indicates reporting agent is introduced into the capillary; however, the specifically also generically state incubating the entire capillary in a detection antibody. Thus, the specification does not impact clarity to this claim limitation.
Claims 2-8 are rejected as being dependent on rejected claim 1.
Claims 11-13 are indefinite. The term “at least approximately” in claims 11-13 is a relative term which renders the claim indefinite. The term “at least approximately” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear to a skilled artisan where the range ends and thus fails to recite objective boundaries that would allow a skilled artisan to practice the full scope of the claimed invention .
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 1, 6, 7, 9, 16, and 20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to nonstatutory subject matter. The claims do not fall within at least one of the four categories of patent eligible subject matter because the claimed invention is directed to an abstract idea 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
Claims 1, 7, 9, and 16 recite "quantifying a relative abundance" and "quantifying a charged variant," in which "quantifying", given the broadest reasonable interpretation, involves dividing the area of an individual peak by the total area under all peaks (claim 7 and para 0095), which is a mathematical concept, specifically a mathematical calculation. More recent opinions of the Supreme Court have affirmatively characterized mathematical relationships and formulas as abstract ideas. See, e.g., Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 573 U.S. 208, 218, 110 USPQ2d 1976, 1981 (2014); Bilski v. Kappos, 561 U.S. 593, 611-12, 95 USPQ2d 1001, 1010 (2010). See MPEP 2106.049(a)(2).
Further, claim 16 recites "generating a charge variant profile," which may refer to the calculated relative abundance (para 0095) and involves plotting data, which involves mathematical calculation and visualizing the mathematical relationship between relative abundance and isoelectric point. A mathematical relationship is a relationship between variables or numbers. A mathematical relationship may be expressed in words or using mathematical symbols. See MPEP 2106.049(a)(2).
Claim 16 further recites "comparing a charge variant profile to the known charge variant profile," which is an abstract mental process. 'The courts consider a mental process (thinking) that "can be performed in the human mind, or by a human using a pen and paper" to be an abstract idea. CyberSource Corp. v. Retail Decisions, Inc., 654 F.3d 1366, 1372, 99 USPQ2d 1690, 1695 (Fed. Cir. 2011). As the Federal Circuit explained, "methods which can be performed mentally, or which are the equivalent of human mental work, are unpatentable abstract ideas the ‘basic tools of scientific and technological work’ that are open to all.’" 654 F.3d at 1371, 99 USPQ2d at 1694 (citing Gottschalk v. Benson, 409 U.S. 63, 175 USPQ 673 (1972)). See also Mayo Collaborative Servs. v. Prometheus Labs. Inc., 566 U.S. 66, 71, 101 USPQ2d 1961, 1965 (2012) ("‘[M]ental processes[] and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work’" (quoting Benson, 409 U.S. at 67, 175 USPQ at 675)); Parker v. Flook, 437 U.S. 584, 589, 198 USPQ 193, 197 (1978) (same). Accordingly, the "mental processes" abstract idea grouping is defined as concepts performed in the human mind, and examples of mental processes include observations, evaluations, judgments, and opinions.' See MPEP 2106.049(a)(2).
Lastly, claims 6 and 20 recite "generating an electropherogram" which would include a "plot of a strength of a signal… versus an isoelectric point," which is a mathematical concept that describes the ratio, or the mathematical relationship, between calculated relative abundance, which the disclosure correlates to strength of a signal (para 0097), and isoelectric point. Thus, these claims recite an abstract idea.
Step 2A, Prong 2
This judicial exception is not integrated into a practical application in claims 1,6, 7, 9, 16, and 20 because measuring a signal that correlates to relative abundance within an isoelectric point is a data collecting step that does not add a meaningful limitation to the abstract idea.
The additional element in claim 16 of assessing levels of environmental stress is insufficient to integrate into practical application because comparing information regarding a sample or test subject to a control or target data has been held to be an “abstract mental process” (see as in University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 113 USPQ2d 1241 (Fed. Cir. 2014) which involved "comparing BRCA sequences and determining the existence of alterations", the collecting and comparing of known information in Classen, the comparing information regarding a sample or test subject to a control or target data in Ambry and Myriad CAFC, as well as Mayo, which also involved specific numerical cutoff levels).
ELIGIBILITY STEP 2B: WHETHER THE ADDITIONAL ELEMENTS
Instant claim 1 does not include additional elements that are sufficient to amount to significantly more than the judicial exception because introducing the analyte into a capillary, separating charge variants using isoelectric focusing, and detecting charge variants using a detection antibody are steps routine and conventional in the art, as taught by Palackal et al (see Palackal PGPub 20200393455 A1, paras 0005, 0049, 0088, 0095 and Fig. 7).
In instant claim 9, the additional elements of reducing and denaturing polypeptides, generating a buffer exchanged sample that includes reduced and denatured polypeptides, and measuring a signal that corresponds to an abundance are not sufficient to amount to significantly more than the judicial exception because these steps are routine and conventional in the art, as taught by Vanam et al (see Vanam et al, Rapid quantitative analysis of monoclonal antibody heavy and light chain charge heterogeneity, 25 August 2015, mAbs, 7 (6), 1118-1127. IDS dated 3/17/23, NPL Ref #1)
The additional elements recited in instant claims 6 and 20 are not sufficient to amount to significantly more than the judicial exception because generating an electropherogram and incubating the capillary in a detection antibody and in a reporter molecule are routine and conventional in the art, as taught by Palackal et al (see Palackal PGPub 20200393455 A1, Figs 9-10).
In instant claim 16, assessing levels of a dependent variable by comparing results to a known reference, amounts to a routine and conventional evaluation process known in the art. For instance, comparing charge variant profiles for a set of charge variants generated pre and post exposure to environmental stress revealed the formation of acidic variants under stress conditions (Cao et al, Charge variants characterization and release assay development for co-formulated antibodies as a combination therapy, mAbs. 2019 Feb 20;11(3):489–499).
For the reasons stated above, claims 1, 6, 7, 9, 16, and 20 stand rejected as being directed to abstract ideas.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-8 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being clearly anticipated by Palackal et al., (PGPub 20200393455 A1).
Throughout the disclosure, Palackal teaches methods for separating variants of target contaminating proteins, which involves separating protein components of a sample by charge along an isoelectric gradient, created with carrier ampholytes, in one or more capillaries using capillary electrophoresis: immobilizing the protein components of the sample within capillaries; contacting the protein components within the capillaries with one or more primary antibodies that specifically bind to the charge variant or multiple charge variants in the sample, thereby detecting and/or discriminating between variants in the sample. Palackal further teaches the use of a chemiluminescent detection system comprising of a horseradish enzyme label and luminol-peroxidase agent to detect the detection antibody and thus detect variants in a sample.
Regarding claim 1, Palackal teaches a method of quantifying a charge variant within an analyte, the method comprising (para 0005, and para 0118): introducing the analyte into a capillary (Fig. 8; para 0049; and para 0005); separating charge variants within the sample buffer along an isoelectric gradient (para 0095, Fig. 8); incubating the capillary in a detection antibody (para 0088; Fig. 8; and para 0118); and quantifying a relative abundance of a charge variant based on a signal that corresponds to the detection antibody (para 0005,and Fig. 7).
Regarding claim 2, Palackal teaches the method of claim 1, further comprising incubating the capillary in a reporter molecule (paras 0012-0013 and Fig. 8).
Regarding claim 3, Palackal teaches the method of claim 2, wherein the reporter molecule comprises an antibody conjugated to horseradish peroxidase or streptavidin conjugated to horseradish peroxidase (para 0089 ; Fig. 9 caption).
Regarding claim 4, Palackal teaches the method of claim 2, further comprising introducing a detection agent into the capillary (para 0088, and Fig. 8).
Regarding claim 5, Palackal teaches the method of claim 4, wherein the detection agent is luminol-peroxide. (para 0088, and para 0089).
Regarding clam 6, Palackal teaches the method of claim 2, further comprising, generating an electropherogram, wherein the electropherogram includes a plot of a strength of a chemiluminescent signal generated by the reporter molecule versus an isoelectric point along the isoelectric gradient where the chemiluminescent signal was detected (Figs. 9-10).
Regarding claim 7, Palackal teaches the method of claim 6, wherein quantifying the relative abundance of the charge variant based on the signal that corresponds to the detection antibody includes calculating an area under a peak of the electropherogram that corresponds to the charge variant (para 0084; Fig. 7).
Regarding claim 8, Palackal teaches the method of claim 1, further comprising, after separating charge variants along the isoelectric gradient, and prior to incubating the capillary in the detection antibody: immobilizing charge variants within the capillary (para 0005, para 0085, and Fig. 8).
Claims 9-13 are rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by Vanam et al (Rapid quantitative analysis of monoclonal antibody heavy and light chain charge heterogeneity, 25 August 2015, mAbs, 7 (6), 1118-1127. IDS dated 3/17/23, NPL Ref #1).
Vanam teaches a method, ChromiCE, which combines capillary isoelectric focusing with another analytical chromatographic technique, for separating a diverse set of charged variants under reducing and denaturing conditions. Vanam further teaches a method for quantifying charged variants of isolated analytes of interest, allowing for quantitative assessment of charge heterogeneity of a sample.
Regarding claim 9, Vanam teaches a method of quantifying a charge variant within an analyte, the method comprising: reducing and denaturing polypeptides within the analyte to generate reduced and denatured polypeptides, wherein the analyte includes charge variants of a target polypeptide (pg. 1122, left column, first full paragraph); buffer exchanging the reduced and denatured polypeptides to generate a buffer exchanged sample, wherein the buffer exchanged sample includes the reduced and denatured polypeptides (pgs. 1123-1124); preparing a sample buffer including the buffer exchanged sample (pg. 1125, para 5); introducing the sample buffer into a capillary (pg. 1125, para 5); separating charge variants of the target polypeptide along an isoelectric gradient (pg. 1119, para 1, Figs. 5A-B); and measuring a signal that is correlated to an abundance of the target polypeptide at a region within the isoelectric gradient within the capillary (pg. 1122, para 2; pg. 1123, Table 1; pg. 1124, Fig. 6; and pg. 1125, para 5; pg.).
Regarding claim 10, Vanam teaches the method of claim 9, wherein the sample buffer includes urea, carrier ampholytes, and a cellulose (pg. 1125, para 5).
Regarding claim 11, Vanam teaches the method of claim 10, wherein the cellulose is hydroxyl propyl methyl cellulose, and the sample buffer includes at least approximately 1 volume percent hydroxyl propyl methyl cellulose (pg. 1125, para 5).
Regarding claim 12, Vanam teaches the method of claim 10, wherein the sample buffer includes a urea concentration of at least approximately 6 M (pg. 1121, para 1 and pg. 1125, para 5).
Regarding claim 13, Vanam teaches the method The method of claim 12, wherein the urea concentration of the sample buffer is at least approximately 8 M (pg. 1125, para 5).
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 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Vanam et al. (Rapid quantitative analysis of monoclonal antibody heavy and light chain charge heterogeneity, 25 August 2015, mAbs, 7 (6), 1118-1127; IDS filed 03/17/2023) in view of Kahle et al. (2018, Electrophoresis, 39, 2492-2511)
Regarding claims 14 and 15, Vanam teaches the method of claim 9, as described above (see Claims Rejections- 35 USC § 102). Vanam differs from the instant claims in failing to teach a sample buffer that includes formamide at a concentration of less than or equal to approximately 30 volume percent.
However, Kahle, in the same field of endeavor, teaches wherein the sample buffer includes formamide (pg. 2495, lines 19-21) and wherein a formamide concentration within the sample is less than or equal to approximately 30 volume percent (pg. 2496, Table 2).
It would have been prima facie obvious for a person having ordinary skill in the art to modify the method taught by Vanam by adding formamide at a concentration of less than or equal to 30 volume percent to the buffer solution as taught by Kahle. . One would be motivated to combine a sample buffer that includes formamide, with a concentration less than or equal to 30 % (v/v)because formamide is a well-known solubility enhancer and denaturant that improves the solubility of difficult-to-solubilize proteins and prevents variant aggregation and precipitation, which could lead to low experimental reproducibility. One would have a reasonable expectation of success in combining the formamide buffer solution taught by Kahle with the method taught by Vanam because Kahle teaches adding less than or equal to 30 % (v/v) formamide in a sample buffer for separating charged variants within a capillary successfully, including improved peak resolution and reproducible results.
Claims 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Cao et al. (Charge variants characterization and release assay development for co-formulated antibodies as a combination therapy, MAbs. 2019 Feb 20;11(3):489–499) in view of Palackal et al., PG Pub 20200393455 A1.
Throughout the disclosure, Cao teaches a method for characterizing charge variants of therapeutic antibodies that are combined to make drug co-formulations. Further, Cao teaches separating charge variants based on charge along a stable pH gradient within a capillary, detecting variants using a UV detector at 280 nm. Cao further teaches generating charge variant profiles. Particularly, Cao teaches a method of assessing levels of stress charge variants may be exposed to throughout the manufacturing process by investigating changes to charge variant profiles of variants before and after exposure to environmental stress.
Regarding claim 16, Cao teaches a method of assessing a level of environmental stress perceived by a sample of a target polypeptide, the method comprising: generating a charge variant profile for the sample, wherein the charge variant profile includes a plurality of peaks, and where each peak: is associated with a corresponding charge variant of the target polypeptide; is associated with an isoelectric point that is equivalent to the isoelectric point of the corresponding charge variant of the target polypeptide; comparing the charge variant profile for the sample to one or more known charge variant profiles; and based on the comparison of the charge variant profile for the sample to the one or more known charge variant profiles, determining a level of environmental stress perceived by the sample (Figs. 1-2, 4; pg. 490, full paragraphs 3-4, top half; Supplemental Tables S1-S2 and Fig. S1).
Cao does not teach the charge variant profile includes a relative peak area that is associated with a relative abundance of the corresponding charge variant of the target polypeptide.
However, Palackal in the same field of endeavor, teaches a method for determining the relative abundance of a variant of interest by measuring the peak area which corresponds to the amount of detection antibody detected (para 0084, lines 32-37).
It would have been prima facie obvious for a person having ordinary skill in the art to combine the method of generating charge variant profiles, taught by Cao, with the quantitation method involving associating area under respective peaks with relative abundance, as taught by Palackal, to assess and quantify degree of change to variant charge profiles for variants exposed to stress. One skilled in the art would be motivated to combine these methods because Cao teaches generating charge variant profiles and comparing results to assess effects of environmental stress on variants, which is a pertinent assessment for quality control management during drug manufacturing. Additionally, a skilled artisan would have a reasonable expectation of success for this combination because determining relative abundance based on peak area is a known and routine technique in the art (see Yan Xu, Capillary Electrophoresis, 1996, The Chemical Educator, Springer-Veralag New York, Inc, Vol. 1, No. 2).
Regarding claim 17, Cao teaches the method of claim 16, wherein the level of environmental stress is associated with a level of thermal stress, a level of stress due to a manufacturing process hold time, or a level of stress due to freeze-thaw cycles (Fig. 2, pg. 490, full paragraph 4, bottom half).
Regarding claim 18, Cao teaches the method of claim 16, wherein the target polypeptide includes an antibody or an adeno-associated virus (Figs. 1-2, pg. 490, full paragraph 2).
Regarding claim 19, Cao teaches claim 16, wherein generating the charge variant profile for the sample includes introducing the sample into a capillary (pg. 497, para 1 “cIEF for charge profiling”); and separating charge variants of the target polypeptide along an isoelectric gradient (pg. 497, para 1 “cIEF for charge profiling”).
Regarding claim 20, Cao teaches claim 19 but Cao does not teach incubating the capillary in a detection antibody and reporter molecule nor generating an electropherogram with a plot of signal strength versus isoelectric point.
However, Palackal teaches the method of claim 19, wherein generating the charge variant profile for the sample further includes: incubating the capillary in a detection antibody (Fig. 8; para 0005, lines 7-11; para 0088, lines 1-9); incubating the capillary in a reporter molecule (paras 0012-013; Fig. 8); and generating an electropherogram, wherein the electropherogram includes a plot of a strength of a signal generated by the reporter molecule versus an isoelectric point along the isoelectric gradient where the signal was detected (Figs. 9-10).
It would have been prima facie obvious for a person having ordinary skill in the art to replace the detection method when separating variants based on charge along a pH gradient taught by Cao with the antibody-labeling detection method taught by Palackal to increase the sensitivity of the detection system. One having ordinary skill in the art would be motivated to replace the detection method of Cao with the labeling detection method of Palackal because it would allow for detection and analysis of variants present in very low concentrations. A skilled artisan would have a reasonable expectation of success because using detection antibodies conjugated to labels for the detection of variants in capillary electrophoresis is a routine solution with a known potential of success and an improved detection method (see Wang et al., Chemiluminescent Immunoassay and Its Applications, Chin J Anal Chem, 2012, 40(1), 3–10.).
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 1-5 and 7-8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 9, and 11-12 of U.S. Patent Application No. 16/880,736 in view of Wang et al (Chemiluminescent Immunoassay and Its Applications, Chin J Anal Chem, 2012, 40(1), 3–10) and evidenced by Yan (Capillary Electrophoresis, 1996, The Chemical Educator, Springer-Veralag New York, Inc, Vol. 1, No. 2). This is a provisional nonstatutory double patenting rejection.
Regarding claims 1-4, all limitations in the instant claims are recited by the reference claims 1, 4, 9, and 11-12 except wherein the reporter molecule comprises an antibody conjugated to horseradish peroxidase or streptavidin conjugated to horseradish peroxidase. The reference claims recite a reporter molecule comprised of an antibody and a detectable label wherein the detectable label comprises a chemiluminescent label but fails to specify that the chemiluminescent label is horseradish peroxidase or streptavidin conjugated to horseradish peroxidase label.
However, Wang, in the same field of endeavor, recites that it is known in the art that horseradish peroxidase (HRP) is one of the most commonly used labeling enzymes for chemiluminescent immunoassays (Wang et al, Chin J Anal Chem, 2012, 40(1), pgs.4).
It would have been prima facie obvious to a person having ordinary skill in the art, before the effective filing date of the claimed invention, to have used an HRP chemiluminescent label because it is one of a finite number of known options and using the HRP label would amount to employing a known technique that is applicable to chemiluminescent immunoassay methods. A skilled artisan would have recognized that applying this known technique of conjugating an antibody with the HRP labeling enzyme would have yielded predictable results. A person having ordinary skill in the art would have a reasonable expectation of success because this is known technique routinely practiced in the art.
Regarding claim 5, the reference claims fail to recite that the detection agent is luminol-peroxide. However, it is known in the art that the HRP labeling enzyme is only detectable if exposed to hydrogen peroxide. Wang recites that luminol, as the enhancer in luminol-peroxide, is one of a finite number of detection agents routinely used to react with the HRP labeling enzyme for purposes of generating a detectable signal in chemiluminescent immunoassay methods (Wang et al, Chin J Anal Chem, 2012, 40(1), pgs.4).
It would have been prima facie obvious, before the effective filing date, to a person having ordinary skill in the art, to add luminol-peroxide as the detection agent to react with the HRP label conjugated to the detection antibody to generate a detectable signal. A skilled artisan would have recognized that applying luminol-peroxide as a known detection agent, from a finite number of known potential solutions in the art, is required for the HRP label to be detected upon binding to its target. A person having ordinary skill in the art would have a reasonable expectation of success because this is a known technique that is routinely and successfully practiced in the art thus has a known potential solution.
Regarding claim 7, all limitations of instant claim 7 are recited by reference claims 1 and 11 except calculating an area under a peak of the electropherogram that corresponds to the charge variant. However, Yan Xu teaches variant concentration is directly related to peak height and a variant concentration can be determined from the peak area (Capillary Electrophoresis, 1996, The Chemical Educator, Springer-Veralag New York, Inc, Vol. 1, No. 2, pg. 13).
It would have been prima facie obvious, before the effective filing date, to a person having ordinary skill in the art, to calculate the area under a peak of an electropherogram, corresponding to a charge variant, to quantify the charge variant. A skilled artisan would have recognized that the amount or abundance of the charge variant is related to the area under its corresponding peak in an electropherogram. A skilled artisan would have a reasonable expectation of success in quantifying the relative abundance by calculating a peak area because this method is routine and common practice in the art.
Regarding claim 8, all limitations of instant claims 1 and 8 are recited by reference claim 1.
Conclusion
All claims are rejected. No claims are allowed.
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/M.L.L./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 January 7, 2026