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 .
Applicant’s amendment and reply filed November 19, 2025 have been received and entered into the case. Claim 3 is canceled; claims 1 – 2 and 4 – 10 are pending and have been considered on the merits. All arguments have been fully considered.
Claim Rejections - 35 USC § 112
Previous rejections under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, are withdrawn to deleting “targeted therapy” from claim 5 and amending claims 6 – 10 to a composition.
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 6 – 10 remain rejected under 35 U.S.C. 102a1 as being anticipated by CN 108949730A (IDS 06.27.2023, FPDb#1) as evidenced by Search Report of SEQ ID NO:2, 2025.
Regarding claims 6 - 8, CN teaches a pharmaceutical composition comprising a mutant collagenase (claims) wherein the collagenase is 100% match to SEQ ID NO:2 (interpreted as “pure”), per the search report performed on 08.14.2025, or is the same as the claimed collagenase.
Although the reference does not teach the composition is for use in making a medicant for cancer treatment or malignant tumor, the use of the composition is regarded as an intended use. The intended use of the claimed composition does not patentably distinguish the composition, per se, since such undisclosed use is inherent in the reference composition. In order to be limiting, the intended use must create a structural difference between the claimed composition and the composition of the prior art. In the instant case, the intended use fails to create a structural difference, thus, the intended use is not limiting. Please note that when applicant claims a composition in terms of function, and the composition of the prior art appears to be the same, the Examiner may make rejections under both 35 U.S.C 102 and 103 (MPEP 2112).
Regarding claims 9 – 10, the composition includes a pharmaceutical carrier (claim 6) and is an injection (claim 7).
The reference anticipates the claimed subject matter.
Response to Arguments
Applicant argues that the mutant collagenase of CN ‘730 does not teach the composition is used for treating cancer and that it has 10% activity of the wild type collagenase.
However, this argument fails to persuade.
CN ‘730 teaches the claimed composition mutant collagen with the claimed SEQ ID with a pharmaceutical carrier that is injected (e.g., injection dosage form). In this regard, the compositions are the same. Moreover, the claims fail to recite any additional component that creates a structural difference in the composition such that it exhibits a structural difference from that of the prior art.
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.
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 – 2 and 4 – 10 remain rejected under 35 U.S.C. 103 as being unpatentable over Dolor et al. (2018, IDS 06.27.2023 NPL #3) in view of CN 108949730A (IDS 06.27.2023 FPD #1).
Regarding claims 1, 6 and 8 – 10, Dolor teaches methods of treating cancer wherein a composition comprising collagenase is injected (with carrier for injections/infusion) into a tumor within a mouse (a subject), wherein collagen in the tumor extracellular matrix (ECM) was reduced (p.2072, Table 1). Dolor does not teach administering a mutant collagenase having the claimed SEQ ID NO:2. However, the reference indicates various collagenases may be used to treat tumors by reducing ECM collagen. In support, Table 1 reflects collagenase from different sources to include Clostridiopeptidase A. Moreover, it would have been obvious to one of ordinary skill in the art to substitute any known collagenase in the methods disclosed by Dolor as a matter of routine practice and with a reasonable expectation for successfully reducing collagentreating a tumor. At the time the claims were filed, the claimed collagenase was known in the art. In support, CN108919730A teaches a recombinant (mutant) clostridopeptidase A with 100% identity to the instantly claimed SEQ ID NO:2 (see search results 08.14.2025). As such, at the time the claims were filed, one of ordinary skill in the art would have been motivated to use the collagenase of CN ‘730 in the methods of Dolor with a reasonable expectation for successfully reducing collagen in the tumor environment and treating cancer.
Regarding claims 2 and 7, the tumors are each solid tumors (Table 1, melanoma, sarcoma, osteosarcoma, or are malignant).
Regarding claim 4, Dolor does not indicate the collagenase is injected by way of two or multipoint injections or in the claimed amount. However, Dolor indicates that collagenase is the active component to reduce collagen in the ECM of the tumor environment (abstract, p.2070 – 2072), or is a recognized result effective variable. In this regard, it would have been obvious to one of ordinary skill in the art to optimize the method of injection as well as the amount of collagenase administered as a matter of routine practice and experimentation.
Regarding claim 5, Dolor teaches the collagenase is administered with other tumor targeting therapies such as IgG (p.2073-2074).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant argues that Dolar teaches Clostridiopeptidase A does not reduce the abundance of collagen in the extracellular matrix of the tumor environment, which is required by the claims, thereby teaching away from the claimed invention; and that the claimed method results in reduction of collagen and ECM loosening which is not disclosed by the cited prior art.
However, this argument fails to persuade. The claims are drawn to a method of cancer treatment wherein the mutant collagenase is injected into a tumor to reduce abundance of collagen. Dolor clearly teaches collagenase reduces tumor collagen (p.2072 – 2073). Table 1 shows various types of collagenases such as Clostridiopeptidase A removes collagen impediment, and does not disclose any of the various collagenases fail to reduce collagen in the tumor microenvironment as argued. Instead, looking to the references summarized in Table 1, Alexandrakis teaches administering bacterial collagenase reduces tumor collagen (p.206); Netti teaches that interstitial resistance and collagen are directly correlated (Figure 5) and that collagenase treatment increased the interstitial diffusion coefficient by 100% (p.2500, Table 1); and Eikenes teaches collagenase increased the interstitial diffusion coefficient in tumor spheroids and tumor tissues (abstract) by reducing collagen content (p.359, 362, 365). Thus, as previously iterated, Dolor, supported by the references summarized therein, expressly teaches bacterial collagenase Clostridiopeptidase A reduces collagen in the tumor microenvironment as claimed.
Applicant appears to suggest that Dolor summarizes “no change in ECM” however applicant fails to indicated where this language is obtained in the reference or that the phrase applies to collagen content in the tumor environment.
Therefore, the claims remain rejected.
No claims are allowed.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUTH A DAVIS whose telephone number is (571)272-0915. The examiner can normally be reached Monday - Friday (8am - 4pm).
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/RUTH A DAVIS/Primary Examiner, Art Unit 1699