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 .
Claim Status
The amendment of 09/15/2025 has been entered. Claims 1, 3, 6, 32, 35, 38, 59-60, and 62-67 are pending (claim set as filed on 09/15/2025). Claims 1, 3, and 6 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant previously elected with traverse invention Group II, drawn to a method of treating and preventing cancer, and further elected DNAJB1 species SEQ ID NO: 7, PRKACA species SEQ ID NO: 8, and the cancer species Fibrolamellar hepatocellular carcinoma (FLC) in the reply filed on 12/24/2024. Claims 32, 35, 38, 59-60, and 62-67 are currently under examination and were examined on their merits.
Withdrawn Objections/Rejections
The objections to the drawings set forth in the previous Office action are withdrawn in light of the amended drawings filed on 09/16/2025.
The claim rejections under 35 U.S.C. 112(a) and under 35 U.S.C. 112(b) set forth in the previous Office action are withdrawn in light of the amendment filed on 09/15/2025.
The claim rejections under 35 U.S.C. 102(a) and 35 U.S.C. 103 set forth in the previous Office action are withdrawn in light of the amendment filed on 09/15/2025. New rejections have been placed, as discussed below.
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.
Claims 32, 38, 59-60, 62-67 are newly rejected as necessitated by amendment under 35 U.S.C. 102(a)(1) as being anticipated by Robine et al. (WO 2015/048367 A1, published on 04/02/2015), as evidenced by Kastenhuber et al. (“DNAJB1–PRKACA fusion kinase interacts with β-catenin and the liver regenerative response to drive fibrolamellar hepatocellular carcinoma”, published on 12/12/2017, PNAS, Vol. 114, No. 50, pages 13076-13084).
Robine et al.’s general disclosure relates to oncogenic fusion proteins and treatment methods for treating gene-fusion associated cancers (see entire document, including abstract).
Regarding claim 32, pertaining to a method of treating or preventing Fibrolamellar hepatocellular carcinoma (FLC) in a subject, Robine et al. teaches a method of treating or preventing cancer in a subject (“The invention also provides a method for treating or preventing a liver cancer in a subject.”, “In some embodiments, the liver cancer comprises fibrolamellar hepatocellular carcinoma”; paragraphs [0085], [00116]), comprising:
administering to the subject an effective amount of a fusion protein comprising a DNAJB1 portion and a PRKACA portion (“In further embodiments, the method comprises administering to the subject an effective amount of a DNA J-cAMP-dependent PK fusion molecule inhibitor, wherein the inhibitor decreases the size of the solid tumor”; “In one embodiment, a DNA J-cAMP-dependent PK fusion molecule inhibitor can be a peptide fragment of a DNA J-cAMP-dependent PK fusion protein that binds to the protein itself.”; “A DNA J-cAMP-dependent PK fusion molecule or inhibitor can be administered to a subject by any means suitable for delivering the DNA J-cAMP-dependent PK fusion molecule or inhibitor to cells of the subject”; “a DNA J-cAMP-dependent PK fusion molecule can include a DNAJBl-PRKACA fusion protein (e.g., comprising the amino acid sequence shown in SEQ ID NO: 1,…)”; paragraphs [0020], [0041], [0071], [00116]), wherein the PRKACA portion comprises instant SEQ ID NO: 8 (VKEFLAKAKEDF) (see SEQ ID NO: 1, positions 71-82, paragraph [0039]);
thereby treating or preventing said FLC in said subject (“The invention also provides a method for treating or preventing a liver cancer in a subject.”, “In one embodiment, the therapeutic molecule to be administered comprises a polypeptide of a DNA J-cAMP-dependent PK fusion molecule, comprising at least about 75%,…, at least
about 99%, or 100% of the amino acid sequence of SEQ ID NO: 1, and exhibits the function of decreasing expression of such a protein, thus treating a gene fusion-associated cancer; paragraphs [0085], [0087], [00116]). The Examiner notes that inhibiting the cancer associated DNAJB1-PRKACA fusion protein by administering an inhibitor as taught by Robine et al. (see above), will prevent cancer since DNAJB1-PRKACA initiates tumors, as evidenced by Kastenhuber et al. (“Here we demonstrate that the Dnajb1–Prkaca gene fusion drives tumorigenesis in mice, and that fusion to DNAJB1 drives FL-HCC initiation more effectively than wild-type PRKACA overexpression. The requirement of the PRKACA kinase domain in tumor initiation establishes the potential utility of kinase inhibitors targeting the fusion.”; see text box in right column on page 13077).
Regarding claim 38, Robine et al. teaches a method of treating or preventing Fibrolamellar hepatocellular carcinoma (FLC) in a subject (“The invention also provides a method for treating or preventing a liver cancer in a subject.”, “In some embodiments, the liver cancer comprises fibrolamellar hepatocellular carcinoma”; paragraphs [0085], [00116]) comprising:
administering a fusion protein to said subject (“In further embodiments, the method comprises administering to the subject an effective amount of a DNA J-cAMP-dependent PK fusion molecule inhibitor, wherein the inhibitor decreases the size of the solid tumor”; “In one embodiment, a DNA J-cAMP-dependent PK fusion molecule inhibitor can be a peptide fragment of a DNA J-cAMP-dependent PK fusion protein that binds to the protein itself.”; “A DNA J-cAMP-dependent PK fusion molecule or inhibitor can be administered to a subject by any means suitable for delivering the DNA J-cAMP-dependent PK fusion molecule or inhibitor to cells of the subject”; “a DNA J-cAMP-dependent PK fusion molecule can include a DNAJBl-PRKACA fusion protein (e.g., comprising the amino acid sequence shown in SEQ ID NO: 1,…)”; paragraphs [0020], [0041], [0071], [00116]);
thereby treating or preventing said cancer in said subject (“The invention also provides a method for treating or preventing a liver cancer in a subject.”, “In one embodiment, the therapeutic molecule to be administered comprises a polypeptide of a DNA J-cAMP-dependent PK fusion molecule, comprising at least about 75%, …, at least about 99%, or 100% of the amino acid sequence of SEQ ID NO: 1, and exhibits the function of decreasing expression of such a protein, thus treating a gene fusion-associated cancer; paragraphs [0085], [0087]). The Examiner notes that inhibiting the cancer associated DNAJB1-PRKACA fusion protein by administering an inhibitor as taught by Robine et al. (see above), will prevent cancer since DNAJB1-PRKACA initiates tumors, as evidenced by Kastenhuber et al. (“Here we demonstrate that the Dnajb1–Prkaca gene fusion drives tumorigenesis in mice, and that fusion to DNAJB1 drives FL-HCC initiation more effectively than wild-type PRKACA overexpression. The requirement of the PRKACA kinase domain in tumor initiation establishes the potential utility of kinase inhibitors targeting the fusion.”; see text box in right column on page 13077),
wherein the fusion protein comprises an isolated fusion protein comprising a DNAJB1 portion and a PRKACA portion (“a DNA J-cAMP-dependent PK fusion molecule can include a DNAJBl-PRKACA fusion protein (e.g., comprising the amino acid sequence shown in SEQ ID NO: 1,…)”; paragraph [0041]), wherein the PRKACA portion comprises instant SEQ ID NO: 8 (VKEFLAKAKEDF) (see SEQ ID NO: 1, positions 71-82, paragraph [0039]).
Regarding claims 59 and 60, pertaining to the fusion protein, Robine et al. teaches wherein the DNAJB1 portion comprises instant SEQ ID NO: 7 (RKREIFDRYGEE) (see SEQ ID NO: 1, positions 59-70, paragraph [0039]).
Regarding claim 62, pertaining to the PRKACA portion of the fusion protein, Robine et al. teaches wherein the PRKACA portion comprises instant SEQ ID NO: 8 (VKEFLAKAKEDF) (see SEQ ID NO: 1, positions 71-82, paragraph [0039]).
Regarding claim 63, pertaining to the fusion protein, Robine et al. teaches wherein the DNAJB1 portion comprises instant SEQ ID NO:7 fused to a PRKACA portion comprising instant SEQ ID NO: 8 (see SEQ ID NO: 1, positions 59-82, paragraph [0039]). The Examiner notes that Robine et al.’s SEQ ID NO:1 comprises the sequence RKREIFDRYGEEVKEFLAKAKEDF (SEQ ID NO: 1, positions 59-82).
Regarding claim 64, pertaining to the method, Robine et al. teaches wherein the subject is identified as suffering from Fibrolamellar hepatocellular carcinoma (FLC), and the fusion protein is administered to the identified subject (“The invention also provides a method for treating or preventing a liver cancer in a subject… In some embodiments, the liver cancer comprises fibrolamellar hepatocellular carcinoma, … In one embodiment, the method comprises detecting the presence of a DNA J-cAMP dependent PK fusion molecule in a sample obtained from a subject, the presence of the fusion being indicative of a liver cancer, and, administering to the subject in need a therapeutic treatment against a liver cancer”, “A DNA J-cAMP-dependent PK fusion molecule or inhibitor can be administered to a subject by any means suitable for delivering the DNA J-cAMP-dependent PK fusion molecule or inhibitor to cells of the subject”; paragraphs [0085], [00116]).
Regarding claims 65 and 66, pertaining to the fusion protein, Robine et al. teaches wherein the DNAJB1 portion comprises instant SEQ ID NO: 7 (RKREIFDRYGEE) (see SEQ ID NO: 1, positions 59-70, paragraph [0039]).
Regarding claim 67, pertaining to the fusion protein, Robine et al. teaches wherein the DNAJB1 portion comprises instant SEQ ID NO:7 fused to a PRKACA portion comprising instant SEQ ID NO: 8 (see SEQ ID NO: 1, positions 59-82, paragraph [0039]). The Examiner notes that Robine et al.’s SEQ ID NO:1 comprises the sequence RKREIFDRYGEEVKEFLAKAKEDF (SEQ ID NO: 1, positions 59-82).
Robine et al. does not teach wherein the DNAJB1-PRAKCA fusion protein is used as a fusion protein vaccine in the prevention/treatment method (instant claims 38, 44, 64-67).
The MPEP states:
"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable.” (MPEP 2112 (I)).
“There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference.” (MPEP 2112(II)).
Since the DNAJB1-PRKACA fusion protein taught by Robine et al. comprises the instantly claimed structure, the fusion protein taught by Robine et al. inherently possesses the instantly claimed cancer vaccine properties. Therefore, Robine et al.’s cancer prevention and treatment method comprising the instantly claimed DNAJB1-PRKACA fusion protein anticipates the claimed cancer prevention and treatment method using DNAJB1-PRCKACA as a cancer vaccine in instant claims 38, 44, 64-67.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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 factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
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.
Claim 35 is newly rejected as necessitated by amendment under 35 U.S.C. 103 as being unpatentable over Robine et al. (WO 2015/048367 A1, published on 04/02/2015), as evidenced by Kastenhuber et al. (“DNAJB1–PRKACA fusion kinase interacts with β-catenin and the liver regenerative response to drive fibrolamellar hepatocellular carcinoma”, published on 12/12/2017, PNAS, Vol. 114, No. 50, pages 13076-13084), in view of Kyi et al. (“Immune Checkpoint Inhibitor Combinations in Solid Tumors: Opportunities and Challenges.”, published on 06/28/2016, Immunotherapy, 8(7), pages 821-837), in further view of Chakrabarti et al. (“Clinicopathological features and outcomes of fibrolamellar hepatocellular carcinoma”, published Jun 2019; 10(3); pages 554-561).
The teachings of Robine et al. are discussed above. However, Robine et al. does not teach the method further comprising administering an immune checkpoint inhibitor to the subject (instant claim 35).
Kyi et al.’s general disclosure relates to “checkpoint inhibitor combination therapy is to improve clinical response and minimize toxicities” (see entire document, including abstract).
Regarding claim 35, Kyi et al. teaches potential synergistic combinations of checkpoint blockade with conventional therapies and newer immunotherapies (“Potential synergistic combinations include checkpoint blockade with conventional (radiation, chemotherapy and targeted therapies) and newer immunotherapies (cancer vaccines, oncolytic viruses, among others)”; see abstract).
Chakrabarti et al.’s general disclosure relates to “clinicopathological features and the outcomes of patients with fibrolamellar hepatocellular carcinoma (FLHCC)” (see entire document, including abstract).
Regarding claim 35, Chakrabarti et al. teaches wherein in select cases of FLHCC, therapy with a checkpoint inhibitor may provide a viable treatment option. (“overall survival (OS)”, “In FLHCC, surgical resection was associated with prolonged OS; …. In select cases, therapy with a checkpoint inhibitor may provide a viable treatment option.”; see abstract). Additionally, Chakrabarti et al. teaches wherein “minimal progress has been made in identifying effective therapeutic regimens for the
management of FLHCC” (page 557, right column, paragraph 3).
While Robine et al. does not teach wherein the method further comprises administering an immune checkpoint inhibitor to the subject (instant claim 35), it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined Robine et al.’s cancer prevention and treatment method with Kyi et al.’s teachings on combination therapy with checkpoint inhibitors and with Chakrabarti et al.’s teachings on treatment of fibrolamellar hepatocellular carcinoma with a checkpoint inhibitor, in order to create a method of treating or preventing cancer in a subject wherein the method further comprises administering an immune checkpoint inhibitor to the subject. One would have been motivated to do so, in order to develop a superior prevention and treatment method for fibrolamellar hepatocellular carcinoma, due to minimal progress in identifying effective therapeutic regimens for fibrolamellar hepatocellular carcinoma, as taught by Chakrabarti et al. above. A skilled artisan would have reasonably expected success in combining Robine et al.’s, Kyi et al.’s, and Chakrabarti et al.’s teachings, since all references are directed to cancer treatment.
Response to Arguments
Applicant has traversed the previous rejections of claims 32-33, 38, 44, and 57-67 under 35 U.S.C. 102 (a)(1), and claim 35 under 35 U.S.C. 103 (remarks, pages 6-8). As discussed above, the previous rejections under §102 (a)(1) and 35 U.S.C. 103 have been withdrawn, and new rejections have been presented in light of Applicant’s amendment of 09/15/2025. Robine et al., Kyi et al., and Chakrabarti et al. are still relied upon in the above rejections. Applicant's arguments filed on 09/15/2025 have been fully considered but they are not persuasive.
In Applicant’s reply, Applicant states that “[n]either Robine et al. nor Kastenhuber et al. teach or disclose SEQ ID NO: 8. Indeed, neither reference teaches or discloses that Applicant's SEQ ID NO: 7 is fused to SEQ ID NO: 8 to form a fusion protein vaccine.” (remarks, page 6).
The Examiner responds that, as discussed above, Robine et al. teaches a fusion protein comprising instant SEQ ID NO: 7 fused to instant SEQ ID NO: 8 (see highlighted sequence in Robine et al.’s SEQ ID NO: 1 below).
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Since Robine et al. teaches the claimed structure, the fusion protein taught by Robine et al. inherently possesses the instantly claimed cancer vaccine properties.
Applicant discusses that “the Office fails to provide any reasonable explanation as to how one of skill in the art would be able to identify Applicant's instantly claimed sequences from Robine's et al., SEQ ID NO: 1. Even assuming that one of skill in the art did have Robine's et al., SEQ ID NO: 1, there is no guidance found in this reference to identify the specific sequence taught by Applicant.” (remarks, page 7).
The Examiner responds that it appears that Applicant intends to claim a fusion protein consisting of SEQ ID NO: 7 fused to SEQ ID NO: 8, or a fusion protein that has additional specific structural properties in addition to SEQ ID NO: 7 and SEQ ID NO: 8. However, if Applicant intends to claim a fusion protein consisting of SEQ ID NO: 7 fused to SEQ ID NO:8, or a fusion protein that has specific structural properties in addition to SEQ ID NO: 7 and SEQ ID NO: 8, these features are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SANDRA ZINGARELLI whose telephone number is (703)756-1799. The examiner can normally be reached M-F 9-5.
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/SANDRA ZINGARELLI/ Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653