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
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08/03/2026 has been entered.
Application status
In response to the previous Office action, a non-Final rejection (mailed on 02/03/2026), Applicants filed a response and amendment received on 08/03/2026. Said amendment canceled Claims 7, 9 and 14, and amended Claims 1 and 8, and added Claims 15-16. Thus, Claims 1-6, 8, 10-13 and 15-16 are at issue and present for examination.
Claim Rejections - 35 U.S.C. § 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.
Claims 1-6, 8, 10-13 and 15-16 are rejected 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failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention, is withdrawn by virtue of Applicants.
Claims 1, 8 and 15-16 (2-6 and 10-13 dependent therefrom) recite “pre-determined amino-acid pattern” which is indefinite. The reason is that [1] the claims and the specification fail to define what a “pattern” is, i.e., it could mean the exact list of sequences, a motif, a table containing myriads of information regarding certain amino acid motifs, etc.; [2] what pre-defines it, and by what algorithms or criteria; and [3] whether the “pattern” is of the affinity peptides alone or of the entire array surface. Using the noted “pattern” without a definition leaves the metes and bounds uncertain and unclear. In the interest of advancing prosecution, the noted phrase is not given a patentable weight.
Claims 1 and 8 (2-6, 10-13 and 15-16 dependent therefrom) recite “is not a random peptide array” which is indefinite. In the instant context where the claims recite “the diagnostic peptide array has a pre-defined amino-acid pattern and is not a random peptide array”, this negative limitation (italicized) only further confounds the boundaries of the excluded subject matter since the “pre-defined amino-acid pattern” as discussed above is unclear. In the relevant art, a person of ordinary skill in the art would have recognized that even though these peptide arrays are called “random”, they are not randomly designed or undefined because these arrays usually contain: [1] sequences that were computationally sampled from sequence space; [2] control epitopes; and [3] the defined affinity-peptide sequences with random sequence peptides in the remainder of the surface (as also disclosed in the instant specification). Taken together, the metes and bounds of the noted phrase is unclear. In the interest of advancing prosecution, the noted phrase is not given a patentable weight.
Claim 1 recites “the set of affinity peptides” in lines 10-11. However, there is no antecedent basis for the noted phrase because the claim first recites “one or more affinity peptides” in line 8. Therefore, it is unclear what “the set” is referring to, i.e., the one or more, a subset, or a larger constructed panel. In the interest of advancing prosecution, the noted phrase is interpreted as “the one or more affinity peptides”.
Claims 15 and 16 recite “excludes peptides having at least 80% sequence identity to known proteome sequences” which is unclear and indefinite. It is unclear how one can determine sequence identity of peptides which are excluded when one does not know what the sequences of known proteome are. Furthermore, metes and bounds of what “known proteome” are unclear because these claims/specification fail to define what this proteome is of, i.e., human, pathogen, ‘any known proteome’ judging from which database and as of what date, etc., and what it contains, and whether “known” includes the target antigen itself. In the interest of advancing prosecution, these claims are interpreted as “wherein the pre-defined amino-acid pattern is configured to contain any amino acid sequence”.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 15-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 15-16 recite newly added phrase, i.e., “the pre-defined amino-acid pattern is configured for epitope diversity and excludes peptides having at least 80% sequence identity to known proteome sequences”. However, the instant specification fails to provide support for the newly inserted limitation of these claims. There is no example, algorithm, or even prophetic statement that the pre-defined amino-acid pattern is filtered at 80% sequence identity cutoff against all known proteome sequences, nor that the pre-defined amino-acid pattern is “configured for epitope diversity” which is distinct from simply spotting the translated hits. In conclusion, the newly added claims 15 and 16 are deemed as ‘new matter’ because they are not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
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 1-6, 8, 10-13 and 15-16 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, wherein the diagnostic peptide array has a pre-defined amino-acid pattern and is not a random peptide array; and detecting binding of antibodies in the biological sample to the set of affinity peptides of the diagnostic peptide array. See above 112(b) rejections of the claim interpretation.
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.
Applicants’ Arguments:
Applicant respectfully submits that Johnston, alone or in combination with Lopez, fails to teach or reasonably suggest the methods as recited in the amended claims for the reasons set forth below.
The Office Action relies on Johnston for an immunosignature peptide array, such as the 10000X, 100000X, 330000X, or 500000X peptide array, that is contacted with a biological sample and used to identify informative peptides that bind to an antibody of interest. See Office Action at pages 4-5. However, Johnston alone or in combination with Lopez, does not teach or reasonably
suggest the methods of detecting an antibody associated with a disease as recited in the amended claims. Amended claim 1 recites methods of detecting an antibody associated with a disease and includes, among other steps, contacting a biological sample with "a diagnostic peptide array comprising the set of affinity peptides, wherein the diagnostic peptide array has a pre-defined amino-acid pattern and is not a random peptide array." Claim 8 is amended similarly. Nowhere does Johnston teach or reasonably suggest the method as recited in the amended claims. To the contrary, Johnston repeatedly characterizes the relied-upon immunosignature arrays as random peptide arrays, including by disclosing that the different peptides may have "random amino acid sequences." See Johnston at [0220]. Thus, Johnston does not teach or reasonably suggest the methods recited in the amended claims.
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. See Lopez at [0016]. Lopez also discloses, in the context of a viral epitope/mimotope screening process, using serum to deplete a phage display library and using affinity-purified antibodies to screen the subtracted library. See Lopez at [0061]. Lopez does not teach or reasonably suggest a diagnostic peptide array comprising a set of affinity peptides translated from informative peptides identified using an immunosignature peptide array. Nor does Lopez teach or reasonably suggest that such a diagnostic peptide array has a pre-defined amino- acid pattern and is not a random peptide array. A person of skill in the art would not look to Lopez's viral mimotope/phage-library screening and know what or how to apply any portion of Lopez to modify Johnston to provide the methods recited in the amended claims, including the step of contacting the biological sample with a diagnostic peptide array comprising the set of affinity peptides, wherein the diagnostic peptide array has a pre-defined amino-acid pattern and is not a random peptide array. At least for the reasons above, Applicant respectfully submits that the cited references, alone or in combination, fail to establish a prima facie case of obviousness of claims 1 and 8 or of the claims that depend therefrom. Applicant respectfully requests withdrawal of the rejection under 35 U.S.C. § 103.
Examiner’s Explanation:
Applicants’ arguments have been fully considered but are not deemed persuasive for the following reasons.
First, the newly added limitations of claims 1, 8 and 15-16 do not distinguish the methods taught by Johnston et al. combined with Lopez et al. because these limitations are not given any patentable weight due to the 112(b) issues noted above.
Second, the use of word “random” in para [0220] by Johnston et al. describes “discovery” library. It is not therefore teaching away from subsequently making a defined panel of the hits based on the methods taught by Johnston et al., i.e., contact a large diverse peptide library with serum → identify differentially bound (informative) peptides → use those peptides and (proteins they point to) as the actionable output → use the selected sequences to be laid down as the assay (the assay is no longer the original random library).
Third, the methods taught by Lopez et al. is analogous art; and requires selection of peptides that bind antibodies of interest, conversion of those hits into defined synthetic peptides, and use those peptides in a diagnostic immunoassay (peptide ELISA that reports on the antibody of interest, see para [0016] and [0061] of Lopez et al.). In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Fourth, as discussed in KSR International Co. v. Teleflex Inc., 550 U.S.--, 82 USPQ2d 1385 (2007), it is considered obvious to combine prior art elements known to be used in equivalent fields of endeavor together into a single combination. Both references address how antibodies in biological samples bind peptide ligands, and how those ligands are used after selection. That is the same field, not an unrelated art.
Fifth, the newly added claims 15-16 do not save the independent claims 1 and 8 as reasons stated above in 112(b) rejection.
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 1-6, 8, 10-13 and 15-16 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, wherein the diagnostic peptide array has a pre-defined amino-acid pattern and is not a random peptide array; and detecting binding of antibodies in the biological sample to the set of affinity peptides of the diagnostic peptide array. See above 112(b) rejections of the claim interpretation.
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.
Applicants’ 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 1-6, 8, 10-13 and 15-16 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 1-6, 8, 10-13 and 15-16 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 instant office action is non-final.
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
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