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 .
Status of Application, Amendments, And/Or Claims
The Applicants amendments/remarks received 10/21/2025 are acknowledged. Claim 28 is amended; claims 6-7, 9-10, 12, 15-19, 26, 29-31 and 33 are canceled; claims 1-5, 8, 11, 13-14, 20-25, 27-28, 32 and 34-35 are pending; claims 2-5 are withdrawn; claims 1, 8, 11, 13-14, 20-25, 27-28, 32 and 34-35 have been examined on the merits.
Information Disclosure Statement
The information disclosure statement submitted on 10/21/2025 has been considered by the examiner; however, the document was submitted as a “Letter specifying the conditions for filing under 37 CFR 1.97” rather than as an IDS, presumably because of the two-page letter preceding the IDS form. Because the document was not submitted as an IDS form, the document can not be properly annotated and cataloged in the electronic system; hence, Applicant is implored to re-submit the IDS form separately from the letter under the normal document type (“Information Disclosure Statement (IDS) Form (SB08)” which is document code “IDS”).
NPL cite 2, i.e., the Clift reference, is lined through because it is already of record - NPL cite on 11/22/2024 IDS.
Drawings
The replacement drawings received 10/21/2025 are objected to for the following reasons:
37 CFR 1.84(i) states "Words must appear in a horizontal, left-to-right fashion when the page is either upright or turned so that the top becomes the right side, except for graphs utilizing standard scientific convention to denote the axis of abscissas (of X) and the axis of ordinates (of Y)." In the instant application, words in Figures 1D; 2A, D, F; 3A-C, K-M; 4A, E-F, L; 5N; 6D, L, P; 7A, I; 8A-B, J; 9A-C; 10A; 11A and 13B, F and I do not appear in a left-to-right hand fashion. Appropriate correction is required.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Response to Arguments
Applicant's arguments filed 10/21/2025 have been fully considered but they are not persuasive. Arguments of the Applicant’s Response on p. 7 regarding the rejection under 35 U.S.C. § 112(b) are moot as the rejection has been withdrawn.
Regarding the objection to the drawings, the replacement drawings received 10/21/2025 do not address the violation of 37 CFR 1.84(i) in the drawings, i.e., that Figures 1D; 2A, D, F; 3A-C, K-M; 4A, E-F, L; 5N; 6D, L, P; 7A, I; 8A-B, J; 9A-C; 10A; 11A and 13B, F and I all comprise text which does not appear in a left-to-right hand fashion; hence, the replacement drawings received 10/21/2025 remain objected to because the drawings do not comply with 37 CFR 1.84(i). Appropriate correction is required.
Claim Rejections - 35 USC § 112
The rejection of claim 28 under 35 U.S.C. § 112(b), as set forth at p. 4 of the previous Office Action, is withdrawn in view of the amendment of the claims.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 8, 11, 13-14, 20-25, 27-28, 32 and 34-35 are rejected under 35 U.S.C. 103 as being unpatentable over Frost et al., US 10328130 (cite A, PTO-892, 1/15/2025; herein “Frost”) in view of Nakanishi et al., 2018 (NPL cite, IDS, 12/2/2022; herein “Nakanishi”) and Clift et al., 2018 (NPL cite, IDS, 11/22/2024; herein “Clift”).
Frost teaches compositions and methods for treating hyaluronan-associated tumors and cancers (Abst.) wherein the tumor can be colorectal (col. 37, l. 19 – col. 38, l. 33). Frost teaches that colorectal tumors with a poor prognosis are associated with elevated levels of hyaluronic acid (HA) and that HA levels correlate with tumor aggressiveness (col. 37, l. 19 – col. 38, l. 33). Frost teaches that hyaluronidase can induce responsiveness to treatment-resistant colon tumors (col. 99, l. 60 – col. 100, l. 9). Frost teaches that these aggressive, treatment-resistant colorectal tumors with a poor prognosis can be treated with a monotherapy of the hyaluronan-degrading enzyme, hyaluronidase (col. 38, ll. 41-45). Frost teaches that the hyaluronidase can be administered at a dosage of 0.02 – 0.5 mg/kg (col. 41, ll. 39-49) and the hyaluronidase can be PEGylated recombinant human hyaluronidase, i.e. PEGrHuPH20 (col. 57, ll. 44-49; also known as PEGPH20 (Fig. 8); also known as Pegvorhyaluronidase alfa (PVHA), see Clift Abst.).
Frost is silent on the morphology of the tumor, e.g. serrated, and does not recite assaying the levels of expression of atypical protein kinase C zeta (PKCζ) and atypical protein kinase C lambda/iota (PKCλ/ɩ); however, a person of ordinary skill in the art at the time of filing would have found it obvious to apply the method of Frost to treat serrated colorectal tumors with a lower expression level of PKCζ and PKCλ/ɩ in view of the disclosure of Nakanishi.
Nakanishi teaches that serrated adenocarcinomas are an aggressive and treatment-resistant form of colorectal cancer which have reduced expression of PKCζ and PKCλ/ɩ (Abst.). Nakanishi teaches that the expression of PKCζ and PKCλ/ɩ can be assayed by immunohistochemistry of PKCζ and PKCλ/ɩ protein levels in patient tissue biopsies (p. 1143, “Human Serrated Tumors Display Reduced Expression of aPKCs”).
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method of treating a serrated tumor in a subject made obvious by Frost in view of Nakanishi comprising determining that the expression of PKCζ and PKCλ/ɩ in a tissue biopsy of the subject is lower than the levels of expression of PKCζ and PKCλ/ɩ in an individual without a serrated tumor and administering a monotherapy of 0.02 – 0.5 mg/kg Pegvorhyaluronidase alfa to the subject because Nakanishi shows that serrated colorectal tumors express lower levels of PKCζ and PKCλ/ɩ and are aggressive and treatment-resistant and have a poor prognosis and Frost teaches that aggressive, treatment-resistant colorectal tumors with a poor prognosis are associated with elevated HA levels and can be treated by administering a monotherapy of 0.02 – 0.5 mg/kg Pegvorhyaluronidase alfa to the subject; therefore, claims 1, 8, 11, 13, 20, 22-25, 28 and 35 are prima facie obvious.
Frost teaches that their method reduces tumor size (col. 16, ll. 12-13; col. 38, ll. 57-60), but does not specifically disclose the amount of reduction in size.
Clift discloses that treating colorectal cancer with Pegvorhyaluronidase alfa monotherapy induced 43% tumor growth inhibition (Abst.).
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious that the method made obvious by Frost in view of Nakanishi would reduce tumor burden by at least 20% wherein tumor burden is average size of tumors and would reduce hyaluronan deposition; therefore, claims 14, 27 and 32 are prima facie obvious.
Regarding claim 21, Nakanishi teaches that the protein levels of PKCζ and PKCλ/ɩ are lower in serrated colorectal tumors; hence, the low levels of expression of PKCζ and PKCλ/ɩ comprises low transcription level or low translation level; therefore, claim 21 is prima facie obvious.
Frost teaches that their method reduces the pericellular matrix of the tumor (col. 16, ll. 54-61); hence, a person of ordinary skill in the art at the time of filing would have found it obvious that the method made obvious by Frost in view of Nakanishi would reduce collagen deposition in the tumor; therefore, claim 34 is prima facie obvious.
Response to Arguments
Regarding the rejection of claims 1, 8, 11, 13-14, 20-25, 27-28, 32 and 34-35 under 35 U.S.C. § 103 over Frost in view of Nakanishi and Clift, Applicant argues (pp. 7-8) that “None of Frost et al., Nakanishi et al. or Clift et al., individually or in combination, provides a link between a specific population of patients, e.g., those having a serrated tumor and reduced expression levels of PKCζ and PKCλ/ɩ, and treatment with an inhibitor of hyaluronan activity or expression (claim 1). Moreover, none of Frost et al., Nakanishi et al. or Clift et al., individually or in combination, provides a link between a specific population of patients, e.g., those having a serrated tumor, and treatment with an inhibitor of hyaluronan activity or expression (claim 22).” This is unpersuasive as the claims are not drawn to providing a link between patients having a serrated tumor and reduced expression levels of PKCζ and PKCλ/ɩ and treatment with hyaluronan inhibitor. The claims are drawn to methods of treating a serrated tumor in a subject wherein the subject has lower levels of expression of PKCζ and PKCλ/ɩ compared to levels of expression of PKCζ and PKCλ/ɩ in an individual without a serrated tumor comprising administering to the subject a therapeutically effective amount of an inhibitor of hyaluronan activity or expression wherein the elected species of an inhibitor of hyaluronan activity or expression is Pegvorhyaluronidase alfa (PVHA).
Frost teaches that colorectal tumors with a poor prognosis are associated with elevated levels of hyaluronic acid (HA); that HA levels correlate with tumor aggressiveness; that hyaluronidase can induce responsiveness to treatment-resistant colon tumors; that these aggressive, treatment-resistant colorectal tumors with a poor prognosis can be treated with a monotherapy of the hyaluronan-degrading enzyme, hyaluronidase, which can be Pegvorhyaluronidase alfa (PVHA) administered at a dosage of 0.02 – 0.5 mg/kg.
Nakanishi teaches that serrated adenocarcinomas are an aggressive and treatment-resistant form of colorectal cancer which have reduced expression of PKCζ and PKCλ/ɩ which can be assayed by immunohistochemistry of PKCζ and PKCλ/ɩ protein levels in patient tissue biopsies.
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method of treating a serrated tumor in a subject made obvious by Frost in view of Nakanishi comprising determining that the expression of PKCζ and PKCλ/ɩ in a tissue biopsy of the subject is lower than the levels of expression of PKCζ and PKCλ/ɩ in an individual without a serrated tumor and administering a monotherapy of 0.02 – 0.5 mg/kg Pegvorhyaluronidase alfa to the subject because Nakanishi shows that serrated colorectal tumors express lower levels of PKCζ and PKCλ/ɩ and are aggressive and treatment-resistant and have a poor prognosis and Frost teaches that aggressive, treatment-resistant colorectal tumors with a poor prognosis are associated with elevated HA levels and can be treated by administering a monotherapy of 0.02 – 0.5 mg/kg Pegvorhyaluronidase alfa to the subject.
Hence, Nakanishi clearly establishes that serrated colorectal tumors express lower levels of PKCζ and PKCλ/ɩ, are aggressive, treatment-resistant and have a poor prognosis and Frost establishes that aggressive, treatment-resistant colorectal tumors with a poor prognosis are associated with elevated HA levels and can be treated by administering a monotherapy of 0.02 – 0.5 mg/kg Pegvorhyaluronidase alfa to the subject; hence, Frost and Nakanishi clearly provide a link between patients having a serrated tumor and reduced expression levels of PKCζ and PKCλ/ɩ and treatment with the hyaluronan inhibitor PVHA, i.e., that serrated tumors in patients with reduced expression levels of PKCζ and PKCλ/ɩ are aggressive, treatment-resistant and have a poor prognosis, which Frost teaches can be treated with PVHA monotherapy. Hence, Applicant’s arguments are unpersuasive and the rejection is maintained.
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, 8, 14, 20, 22-23, 27-28, 32 and 34-35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 353-354, 364 and 365 of copending Application No. 17312855 (reference application; herein “’855”).
Although the claims at issue are not identical, they are not patentably distinct from each other because claim 353 of ‘855 recites a method for treating a subject having a disease or condition, comprising: determining a decreased expression level of PKCζ and PKCλ/ɩ in a biological sample obtained from the subject compared to an expression level of PKCζ and PKCλ/ɩ in an individual who does not have the disease or condition; and administering to the subject a therapeutically effective amount of a programmed-death ligand 1 (PD-L1) inhibitor, wherein the disease or condition comprises a disease or condition characterized by serrated polyps in an intestine or by serrated adenocarcinoma; claim 354 of ‘855 recites the method of claim 353, further comprising: determining an increased expression level of hyaluronan in the biological sample compared to an expression level of hyaluronan in an individual who does not have the disease or condition; and administering to the subject a therapeutically effective amount of a hyaluronan inhibitor; claim 364 of ‘855 recites the method of claim 354, wherein the hyaluronan inhibitor is selected from the group consisting of an antagonist of CD44, an antibody inhibitor of CD44, a small molecule inhibitor of CD44, an agonist of hyaluronidase, pegvorhyaluronidase alfa (PVHA), an exogenous hyaluronidase, a recombinant hyaluronidase, and any combination thereof; and claim 365 of ‘855 recites the method of claim 353, wherein the biological sample comprises blood, blood plasma, sera, or tissue biopsy; therefore, claims 1, 8, 20, 22-23, 28 and 35 are prima facie obvious over claims 353-354, 364 and 365 of ‘855.
Regarding claims 14, 27, 32 and 34, the claims do not add additional steps or limitations to the method, rather, they recite hoped-for outcomes which would be achieved by practicing the method made obvious by claims 353-354, 364 and 365 of ‘855; therefore, claims 14, 27, 32 and 34 are prima facie obvious over claims 353-354, 364 and 365 of ‘855.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Regarding the provisional rejection of claims 1, 8, 14, 20, 22-23, 27-28, 32, and 34-35 on the ground of nonstatutory double patenting over claims 353-354, 364 and 365 of copending application No. 17/312,855, Applicant asserts “Application No. 17/312,855 is not yet allowed and so it is premature to consider whether or not to file a terminal disclaimer in the present application.” on p. 7 of the Remarks. The rejection is maintained.
Conclusion
No claims are allowed.
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 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 Trent R Clarke whose telephone number is (571)272-2904. The examiner can normally be reached M-F 10-7 MST.
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, Melenie Gordon can be reached at 571-272-8037. 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.
/TRENT R CLARKE/ Examiner, Art Unit 1651
/DAVID W BERKE-SCHLESSEL/ Primary Examiner, Art Unit 1651
Prosecution Insights