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 .
DETAILED ACTION
Application status
In response to the previous Office action, a non-Final rejection (mailed on 05/08/2025), Applicants filed a response and amendment received on 11/07/2025. Said amendment canceled Claim 9, and amended Claims 1, 7-8, 10-12 and 14. Thus, Claims 1-8 and 10-14 are at issue and present for examination.
Claim Rejections - 35 U.S.C. § 112 - WIHTDRAWN
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 previous rejection of Claims 1, 7, 8 and 14 under 35 U.S.C. § 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention, is withdrawn by virtue of Applicants.
Claim Rejections - 35 U.S.C. § 102 - WITHDRAWN
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.
The previous rejection of Claims 8 and 10-14 under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by Johnston et al. (US PG PUB 2015/0241420, see IDS) is withdrawn because Applicants have inserted the limitation of claim 9 into claim 8.
Claim Rejections - 35 U.S.C. § 103 - MAINTAINED
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.
Claim 1-8 and 10-14 are rejected under 35 U.S.C. 103 as being unpatentable over Johnston et al. (US PG PUB 2015/0241420, see IDS) in view of Lopez et al. (US PG PUB 2004/0014028).
The instant claims are drawn to a method of detecting an antibody associated with a disease or condition of interest, comprising: contacting an immunosignature peptide array with a biological sample from an individual, wherein the immunosignature peptide array comprises peptides that bind to an antibody of interest; detecting binding of the antibody of interest in the biological sample to the peptides of the immunosignature peptide array, thereby identifying a set of informative peptides that bind to the antibody of interest; translating the set of informative peptides to one or more affinity peptides that bind the antibody of interest; contacting the biological sample with a diagnostic peptide array comprising the set of affinity peptides; and detecting binding of antibodies in the biological sample to the set of affinity peptides of the diagnostic peptide array.
Johnston et al. teach a method of screening therapeutic targets, comprising: contacting an immunosignature peptide array with a biological sample from an individual, i.e., serum, wherein the immunosignature peptide array (i.e., 10000X, 100000X, 330000X or 500000X peptide array, see claims 35-38) comprises peptides that bind to an antibody of interest; detecting binding of the antibody of interest in the biological sample to the peptides of the immunosignature peptide array, thereby identifying a set of informative peptides that bind to the antibody of interest; translating the set of informative peptides to one or more affinity peptides that bind the antibody of interest; and constructing a diagnostic peptide array comprising the set of affinity peptides (see para [0170]; [0190]; [0205]; [0170]-[0206]; and claims),
wherein translating comprises probing the biological sample with the antibody of interest to find an original antigen target, and obtaining the peptide sequence of the original antigen target (see para [0045]),
wherein translating comprises creating a library of variants (i.e., construction and probing of PA-X frameshift array) on an informative peptide, and screening binding of the antibody of interest to the variants (see para [0179]), wherein translating comprises aligning the peptide sequence of an informative peptide against proteome sequences (see para [0011] and [0045]),
wherein the condition of interest is a lung cancer, leukemia, pancreatic cancer, prostate cancer, breast cancer, bladder cancer, endometrial cancer and colon and rectal cancer, Type 1 diabetes, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, systemic lupus erythematosus, psoriasis, and scleroderma (see claims 45, 61 and 62),
wherein the diagnostic peptide array further comprises random sequence peptides or peptides (i.e., 10000X, 100000X, 330000X or 500000X peptide array) with insignificant binding to an informative antibody (see claims 35-38).
Johnston et al. do not teach the last step of claim 1, i.e., detecting binding of antibodies in the biological sample to the set of affinity peptides of the diagnostic peptide array, and claim 2, i.e., wherein translating comprises obtaining the antibody of interest by: reverse-engineering the antibody of interest using the peptide sequence of an informative peptide, or affinity purifying the antibody of interest using an informative peptide.
Lopez et al. teach a method of using the epitopes/mimotopes to affinity purify antibodies from immune serum, and detecting the binding of the purified antibodies to screen the library (see Figure 2, and its description on page 4, para [0061]).
It would have been obvious to a person of ordinary skill in the art (POSITA) prior to the effective filing date of the claimed invention to practice the method taught by Johnston et al. and detect the binding of the antibodies, which are affinity purified, to the set of affinity peptides of the diagnostic peptide array as taught by Lopez et al. A POSITA would have been motivated to practice such methods in order to validate if the affinity peptide they discovered in the immunosignature array can indeed bind the antibody which is affinity purified. A POSITA would have had a reasonable expectation of success to practice such methods because all of the required biochemical reagents/material and techniques were rampantly practiced as evidenced by Johnston et al. and Lopez et al. For the reasons provided herein, the invention as claimed is prima facie obvious over the combined teachings of the prior art.
Applicant’s Arguments:
Applicants argue that Johnston teaches "methods and devices to provide efficient methods and systems for discovering therapeutic targets, novel antigens, and for deciphering an immunosignature." Johnston at Abstract. Johnston teaches methods including steps of "a) contacting a peptide array with a first biological sample from an individual with a known condition of interest; b) detecting binding of antibodies in the first biological sample with the peptide array to obtain a first immunosignature profile." Johnston at [0003]. Nowhere does Johnston teach or reasonably suggest a method of detecting an antibody associated with a disease or condition of interest by detecting binding of antibodies in the biological sample to the set of affinity peptides of the diagnostic peptide array. Further, as acknowledged by the Examiner on page 6 of the Office Action, Johnston does not teach or reasonably suggest a method of creating a diagnostic peptide array for a disease or condition of interest, wherein translating comprises obtaining the antibody of interest by reverse-engineering the antibody of interest using the peptide sequence of an informative peptide, or affinity purifying the antibody of interest using an informative peptide. Thus, Johnston does not teach or reasonably suggest the methods of amended claims 1 and 8.
The deficiencies of Johnston are not cured by Lopez. Lopez discloses a method for discriminating between epitopes that induce neutralizing antibodies from those that induce non- neutralizing antibodies. Lopez at [0016]. Therefore, Lopez discloses a method for identifying neutralizing or protective epitopes (different fragments of the different molecules of the pathogen) for designing better vaccines. In contrast, the advantage of the methods presented herein is that the target antigen and/or epitopes do not need to be identified. Specification at [0075]. The present methods use an immunosignature peptide array, where the amino acid sequences of the peptides are randomly selected, for example from random sequence space. Therefore, the advantage of the present invention is that they enable the screening of "[n]ormal, mutated, post-translationally modified, and mimetic epitopes corresponding to any disease or organism" on the same microarray. Specification at [0077]. Therefore, a person of skill in art would not look to Lopez or know what or how to apply any portion of Lopez to Johnston and doing so in an unguided way would not provide an expectation of success. At least for the reasons above, Applicant respectfully submits that the cited references, even if combined, fail to establish a prima facie case of obviousness of claims 1 and 8 or of the claims that depend therefrom.
Examiner’s Explanation:
Applicants’ arguments have been fully considered but are not deemed persuasive for the following reasons. Contrary to Applicants’ allegation, Johnston et al. teach a method of screening therapeutic targets, comprising: contacting an immunosignature peptide array with a biological sample from an individual, i.e., serum, wherein the immunosignature peptide array (i.e., 10000X, 100000X, 330000X or 500000X peptide array, see claims 35-38) comprises peptides that bind to an antibody of interest; detecting binding of the antibody of interest in the biological sample to the peptides of the immunosignature peptide array, thereby identifying a set of informative peptides that bind to the antibody of interest; translating the set of informative peptides to one or more affinity peptides that bind the antibody of interest; and constructing a diagnostic peptide array comprising the set of affinity peptides (see para [0170]; [0190]; [0205]; [0170]-[0206]; and claims), wherein the condition of interest is a lung cancer, leukemia, pancreatic cancer, prostate cancer, breast cancer, bladder cancer, endometrial cancer and colon and rectal cancer, Type 1 diabetes, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, systemic lupus erythematosus, psoriasis, and scleroderma (see claims 45, 61 and 62).
In addition, contrary to Applicants’ allegation that the Lopez reference do not remedy the deficiency of the Johnston reference, and that the target antigen and/or epitopes do not need to be identified, Lopez et al. teach a method of using the epitopes/mimotopes to affinity purify antibodies from immune serum, and detecting the binding of the purified antibodies to screen the library (see Figure 2, and its description on page 4, para [0061]). As such, Lopez et al. are NOT interested in identifying the epitopes as argued by Applicants, but Lopez et al. teach detection and identifying what the purified antibodies. As such, it would have been obvious for one of skill in the art to detect/identify affinity purified antibodies as taught by Lopez et al. in order to validate if the affinity peptide they discovered in the immunosignature array as taught by Johnston et al. can indeed bind the antibody which are affinity purified.
For the reasons provided herein, the invention as claimed is prima facie obvious over the combined teachings of the prior art.
Double Patenting - MAINTAINED
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 1-8 and 10-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10900975 in view of Johnston et al. (US PG PUB 2015/0241420, see IDS) and Lopez et al. (US PG PUB 2004/0014028) since the claims, if allowed, would improperly extend the "right to exclude" already granted in the patent.
Claim 1 of the instant application:
Claim 1. A method of detecting an antibody associated with a disease or condition of interest, comprising: contacting an immunosignature peptide array with a biological sample from an individual, wherein the immunosignature peptide array comprises peptides that bind to an antibody of interest; detecting binding of the antibody of interest in the biological sample to the peptides of the immunosignature peptide array, thereby identifying a set of informative peptides that bind to the antibody of interest; translating the set of informative peptides to one or more affinity peptides that bind the antibody of interest; contacting the biological sample with a diagnostic peptide array comprising the set of affinity peptides; and detecting binding of antibodies in the biological sample to the set of affinity peptides of the diagnostic peptide array.
Claims 1 and 7 of ‘975 patent:
Claim 1. A method of identifying an epitope recognized by an antibody, the method comprising the steps of: (a) contacting a sample comprising the antibody to a plurality of peptides immobilized on an array, wherein the array comprises at least 10,000 peptide features per 1 cm.sup.2, wherein the peptides are spaced no more than 3 nm apart, wherein 95% of the peptides are in a range of 8 amino acids and 14 amino acids, and wherein the peptides are selected without a priori assuming a set of eliciting proteins or proteome; (b) identifying peptides that bind to the antibody with a K.sub.d of less than 10.sup.−7 M; and (c) screening peptide sequences of the identified peptides for a consensus sequence motif, wherein the motif corresponds to an epitope of an antigen to which the antibody specifically binds.
Claim 7. The method of claim 1, further comprising identifying a protein target of the antibody, comprising: (i) searching a protein sequence database for proteins that contain sequences homologous to the consensus sequence motif; (ii) identifying proteins from step (i); and (iii) verifying that the antibody binds to a protein retrieved from the database search.
As shown above in claims 1 and 7 of the ‘975 patent, these claims read on the instant claims 1 and 8, with the specific translating methods recited in claims 3, 5, 10 and 12. Claims 6-7 and 13-14 are included in this rejection because ‘975 patent further teach that the condition of interest includes “cancer, inflammation, autoimmune, cardiovascular, and infectious diseases” (see column 1, lines 32-33), and that the peptide array comprises at least 10,000 peptide (i.e., 10000X, 100000X, 330000X or 500000X peptide array, see claims 1 and 35-38), which comprises random peptides with insignificant binding. The instant claim 1 and the claims of ‘975 patent differ in that claims of ‘975 patent do not recite a specific translating step, which pertains to claims 2, 4 and 11. However, these translating steps are taught by Johnston et al. and Lopez et al. as described above. Lopez et al. teach a method of using the epitopes/mimotopes to affinity purify antibodies from immune serum, and detecting the binding of the antibodies to screen the library (see Figure 2, and its description on page 4, para [0061]), while Johnston et al. teach a translating step which comprises creating a library of variants on an informative peptide, and screening binding of the antibody of interest to the variants (see para [0179]).
Taken together, it would have been obvious for a POSITA to practice the method taught by ‘975 patent and combine the specific translating steps taught by Johnston et al. and Lopez et al. A POSITA would have been motivated to practice such methods in order to validate if the affinity peptide/variants they discovered in the immunosignature array can indeed bind the antibody which is affinity purified. A POSITA would have had a reasonable expectation of success to practice such methods because all of the required biochemical reagents/material and techniques were rampantly practiced as evidenced by ‘975 patent, Johnston et al. and Lopez et al. For the reasons provided herein, claims 1-14 are rejected on the ground of nonstatutory double patenting to prevent the unjustified or improper timewise extension of said patent.
Applicant’s Arguments:
Applicant respectfully disagrees and submits that the amended claims are patentably distinct from the claims of the reference patent, as none of the claims of the reference patent recite the features recited in the amended claims. Accordingly, withdrawal of the rejection is respectfully requested.
Examiner’s Explanation:
Applicants’ arguments have been fully considered but are not deemed persuasive for the following reasons. Applicants’ argument stating that they disagree with the instant rejection is noted. However, for the reasons stated above in the body of the instant rejection, the instant claims 1-8 and 10-14 would have been obvious to a POSITA based on all the claims of the ‘975 patent in view of Lopez et al., and therefore, the instant claims are rejected on the ground of nonstatutory double patenting to prevent the unjustified or improper timewise extension of said patent.
Conclusion
Claims 1-8 and 10-14 are rejected for the reasons as stated above. Applicants must respond to the objections/rejections in this Office action to be fully responsive in prosecution.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee 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 JAE W LEE whose telephone number is (571)272-9949. The examiner can normally be reached on M-F between 9:00-6:00.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached on (571)272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAE W LEE/
Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656