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
Claims 1-3 and 14-117 are cancelled. Claims 4-13 are pending. Claims 4-13 are currently under consideration for patentability under 37 CFR 1.104.
Priority
This application is a 371 of PCT/US2022/030168 filed on 05/20/2022 which claims benefit of PRO 63/191,551 filed on 05/21/2021.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 4-13 have an effective filing date of 05/21/2021 corresponding to PRO 63/191,551.
Information Disclosure Statement
The information disclosure statement filed 11/21/2023 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered. Legible copies of foreign patent documents WO 2005/004903 A1, WO 2018/150326 A1, and WO 2020/076817 A1 were not provided.
Notably, the disclosure statement filed lists a Search Report. The listing of the references cited in a Search Report itself is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the Search Report have not been considered. Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Note: If copies of the individual references cited on the Search Report are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
A signed copy of the Information Disclosure Statement is enclosed. All references are considered unless marked with strikethrough.
Drawings
The drawings 1 and 5-6 filed on 11/21/2023 are accepted. The drawings 2-4 and 7 filed on 11/21/2023 are objected to because Figures 2, 3, and 4 fail to label x-axes and Figure 7 contains “F. nucleatum + metronidazole” that is not specified in the drawing description within the specification. 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.
Specification
The abstract of the disclosure does not commence on a separate sheet in accordance with 37 CFR 1.52(b)(4) and 1.72(b). A new abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text.
The use of the term GenBank, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Interpretation
Claim 6 depends on claim 1, a cancelled claim. For the basis of claim interpretation, reference to “claim 1” will be treated as “claim 4”.
Claim Rejections - 35 USC § 112(a)
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claim 4-13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because a method of treating a cancer in a subject in need thereof comprising administering to the subject a DNase enzyme and an immunomodulator (Claim 4, lines 1-3), while being enabling for inhibiting and relieving certain types of cancer, does not reasonably provide enablement for inhibiting, relieving, and preventing all cancer (Specification, Definitions, Pg. 9, Paragraph 0045). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation’.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed most recently in Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008). See also In re Cortright, 49 USPQ2d 1464, 1466 and Bristol-Myers Squibb Co. v. Rhone-Poulenc Rorer Inc., 49 USPQ2d 1370.
The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: (1) the nature or the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. When the above factors are weighed, it is the examiner’s position that one skilled in the art could not practice the invention without undue experimentation. Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444.
(1) The nature of the invention
Claim 4 is drawn to a method of treating a cancer in a subject in need thereof comprising administering to the subject a DNase enzyme and an immunomodulator. Based on the special definition given in the specification, the treatment of cancer includes cancer prevention (Specification, Definitions, Pg. 9, Paragraph 0045, “preventing, delaying, or reducing the incidence and/or likelihood of the appearance of at least one clinical or sub-clinical symptom of the state, disorder or condition developing in a subject that may be afflicted with or predisposed to the state, disorder or condition, but does not yet experience or display clinical or subclinical symptoms of the state, disorder or condition”). As such, the claim generally reads on prevention of all cancers, the full scope of which is not enabled by the method as instantly claimed.
According to Potter et al., cancer can be random in nature, making it incredibly difficult to prevent the formation of cancer in its entirety (Pg. 974, Introduction). In addition to spontaneous mutations, “many agents, including radiation, chemicals, and viruses” can induce cancer formation i.e. cancer does not have one cause (Cooper, Causes of Cancer, first paragraph). “Chemoprevention employs pharmaceutical agents to reduce the likelihood of disease progression… we have a multiplicity of theories of carcinogenesis that do not provide clear understanding of what is causal and, thus, an incomplete understanding of the role these agents might play in cancer. As a result, cancer chemoprevention is an almost universal failure” (Potter, Pg. 974, Introduction, paragraphs 1-3).
Claim 4 is not enabled because a person having ordinary skill in the art as of the effective filing date of the application would not be able to prevent all cancer predictably and reliably. Claims 5, 7, and 13 are included in this rejection as they depend and/or incorporate claim 4. In addition, since reference to cancelled claim 1 is being treated as reference to claim 4, claims 6 and 8-12 are included in this rejection as they depend and/or incorporate claim 4 (see claim interpretation).
(5) The breadth of the claims
Claim 4 is drawn to a method of treating a cancer in a subject in need thereof comprising administering to the subject a DNase enzyme and an immunomodulator. As such, the claim generally reads on the treatment of any and all cancer, the full scope of which is not enabled by the method as instantly claimed.
While the state of the art is relatively high with regard to the treatment of specific cancer types, the state of the art with regard to treating cancer broadly is underdeveloped. In particular, there is no known anticancer agent that is effective against all cancer cell types. Even within a given cancer type, “[i]ntertumor and intratumor heterogeneity are important obstacles to overcome when designing the most effective therapeutic strategies for patients with cancer. The genotypic and phenotypic variability of tumors can have important consequences for diagnosis, prognosis, and treatment” (Lovly et al., Pg. e586, Integrating the Heterogeneity of Cancer in Clinical Decision Making, first paragraph).
Claim 4 is not enabled because a person having ordinary skill in the art as of the effective filing date of the application would not be able to treat any and all cancer. Claims 5, 7, and 13 are included in this rejection as they depend and/or incorporate claim 4. In addition, since reference to cancelled claim 1 is being treated as reference to claim 4, claims 6 and 8-12 are included in this rejection as they depend and/or incorporate claim 4 (see claim interpretation).
(8) The quantity of experimentation necessary
Claim 4 is drawn to a method of treating a cancer in a subject in need thereof comprising administering to the subject a DNase enzyme and an immunomodulator. As such, the claim generally reads on all immunomodulators (i.e. small molecules, antibodies, etc..), the full scope of which is not enabled by the method as instantly claimed.
In the specification, Figure 7 shows administration of anti-CTLA-4 antibodies and DNase I can prevent toxicity associated with checkpoint inhibitor treatment. In addition, Figure 4 shows that tumors injected with DNase I and an immunomodulator from a group consisting of anti-CTLA-4, anti-PD-1, or anti-OX-40 antibodies reduce the number of TAMs.
The specification does not provide any additional examples or guidance on how to use DNase in combination with immunomodulators outside of anti-CTLA-4, anti-PD-1, and anti-OX-40 antibodies to treat cancer as recited in the claim. The amount of experimentation would not be reasonable because it would require determining which immunomodulator to use in combination with DNase to treat cancer. Immunomodulators comprise a diverse class of molecules including but not limited to corticosteroids, checkpoint inhibitors, T-cells, antibodies, and vaccines. It is not routine to determine how such a broad class of molecules will treat cancer with DNase.
Claim 4 is not enabled because a person having ordinary skill in the art as of the effective filing date of the application would not be able to treat cancer using all immunomodulators with DNase. Claims 5, 7, and 13 are included in this rejection as they depend and/or incorporate claim 4. In addition, since reference to cancelled claim 1 is being treated as reference to claim 4, claims 6 and 8-12 are included in this rejection as they depend and/or incorporate claim 4 (see claim interpretation).
Claim Rejections - 35 USC § 112(b)
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 following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 4-13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 4 recites the limitation "a second immunomodulator" in the last line of claim 4. There is insufficient antecedent basis for this limitation in the claim as “a first immunomodulator” is not appropriately indicated. Claims 5, 7, and 13 are included in this rejection as they depend and/or incorporate claim 4. In addition, since reference to cancelled claim 1 is being treated as reference to claim 4, claims 6 and 8-12 are included in this rejection as they depend and/or incorporate claim 4 (see claim interpretation).
Claim 5 recites the limitation "the tumor associated macrophages (TAMs) and/or tumor infiltrating neutrophils (TINs)" in the last two lines of claim 5. There is insufficient antecedent basis for this limitation in the claim.
Claim 6 depends on claim 1, a cancelled claim, and is therefore rejected as incomplete (see MPEP 608.01[n][v]) because it is not clear what limitations are set forth in claim 1. Claims 8-12 are included in this rejection as they depend and/or incorporate claim 6.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 6 and 8-12 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 6 depends on claim 1, a cancelled claim, and is therefore rejected as incomplete (see MPEP 608.01[n][v]). Claims 8-12 are included in this rejection as they depend and/or incorporate claim 6. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
(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.
Claims 4 and 6-11 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by WO 2014/153150 A1 (herein after referred to as “Lee et al.”).
With regard to claim 4, Lee et al. teach a method of treating a cancer in a subject in need thereof (Pg. 26, Paragraph 0072, "[a]ll of the methods described above may be used in combination… for the treatment of cancer"), comprising administering to the subject an effective amount of a deoxyribonuclease (DNase) enzyme (Pg. 25, Paragraph 0070, "DNase I") and a second immunomodulator (Pg. 25, Paragraph 0070) such as "anti-CTLA-4 antibody".
With regard to claim 6, Lee et al. further teach
With regard to claim 7, Lee et al. further teach the method of claim 4 (see above), wherein the second immunomodulator is a modulator of an immune checkpoint module CTLA-4 (Pg. 26, Paragraph 0072, "anti-CTLA-4 antibody").
With regard to claim 8, Lee et al. further teach the method of claim 6 (see above), wherein the immune checkpoint modulator is an immune checkpoint inhibitor (Pg. 26, Paragraph 0072, "anti-CTLA-4 antibody").
With regard to claims 9-10, Lee et al. further teach the method of claim 8 (see above), wherein the immune checkpoint inhibitor is an antibody that specifically binds CTLA-4 (Pg. 26, Paragraph 0072, "anti-CTLA-4 antibody").
With regard to claim 11, Lee et al. further teach the method of claim 8 (see above), wherein the immune checkpoint inhibitor is selected from ipilimumab or tremelimumab (Pg. 25, Paragraph 0070, "anti-CTLA-4 antibody [e.g., ipilimumab, tremelimumab]").
Accordingly, Lee et al. anticipate instant claims 4 and 6-11.
Claim 5 is rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Lee et al. as evidenced by Ireland & Oliver (Ireland & Oliver, Neutrophils Create an ImpeNETrable Shield between Tumor and Cytotoxic Immune Cells, Immunity, Volume 52, Issue 5, 2020, Pages 729-731).
Lee et al. teach the method of claim 4. However, with regard to claim 5, Lee et al. do not explicitly disclose that DNase is effective to reduce the number and/or activity of the tumor associated macrophages (TAMs) and/or tumor infiltrating neutrophils (TINs) in the immunosuppressive tumor cell microenvironment.
Moreover, “[a] chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present” (MPEP 2112.01). This function is an inherent characteristic of DNase, inseparable from its chemical structure.
“To serve as an anticipation when the reference is silent about the asserted inherent characteristic, such gap in the reference may be filled with recourse to extrinsic evidence” (MPEP 2131.01).
Ireland & Oliver teach that the administration of the DNase enzyme is effective to reduce the activity of TINs in the immunosuppressive tumor cell microenvironment (Pg. 730, Fig. 1, Legend, "Human neutrophils form neutrophil extracellular traps (NETs)… Blocking NET formation via pharmacological PAD4 inhibitors, DNAse-I, Pertussis-toxin (Ptx), or CXCR1 and −2 inhibitors allows tumor cell contact with cytotoxic immune cells").
The reduction of TIN activity by DNase would have been known by a person having ordinary skill in the art prior to the effective filing date of the application. The reference by Ireland & Oliver serves as evidence of an intrinsic property of DNase.
Accordingly, Lee et al. as evidenced by Ireland & Oliver anticipate instant claim 5.
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.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. as applied to claims 4 and 6-11 in view of WO 2020/214820 A3 (herein after referred to as “Fukuda et al.”).
Lee et al. teach:
a method of treating a cancer in a subject in need thereof (Pg. 26, Paragraph 0072, "[a]ll of the methods described above may be used in combination… for the treatment of cancer"), comprising administering to the subject an effective amount of a deoxyribonuclease (DNase) enzyme (Pg. 25, Paragraph 0070, "DNase I") and a second immunomodulator (Pg. 25, Paragraph 0070, "anti-CTLA-4 antibody") (see claim 4).
the second immunomodulator is an immune checkpoint modulator (Pg. 26, Paragraph 0072, "anti-CTLA-4 antibody") (see claim 6). Reference to claim 1 is treated as reference to claim 4 (see claim interpretation).
the immune checkpoint modulator is an immune checkpoint inhibitor (Pg. 26, Paragraph 0072, "anti-CTLA-4 antibody") (see claim 8).
Lee et al. do not teach that the immune checkpoint inhibitor is pembrolizumab, an anti-PD-1 antibody.
Fukuda et al. teach that the immune checkpoint inhibitor is pembrolizumab (Pg. 51, Line 25-28, "the methods of treatment described herein may be performed in combination with administration to the subject: an immune checkpoint modulator (e.g., a PD-1 [programmed cell death 1] antagonist… pembrolizumab").
Fukuda et al. performed experiments on mice wherein “[i]n some experiments, 50 µL of DNase I… was administered intratumorally every other day from 2 to 18 days after [dendritic cell] vaccination. For anti-PD-1 treatment experiments, WT mice were administered 250 mg of anti-PD-1 antibody… intraperitoneally on days 5, 8, 11, and 14” (Pg. 58, Lines 20-25). It is unclear whether DNase I and anti-PD-1 antibody were given separately or together.
Fukuda et al. state, “[i]n some embodiments, the immune checkpoint modulator is an antibody that specifically binds to PD-1” or “an antibody that specifically binds to CTLA-4” (Pg. 4, Lines 27-32, “), indicating the antibodies can be interchanged.
Both anti-PD-1, specifically pembrolizumab, and anti-CTLA-4 antibodies were known and used prior to the effective filing date of the application.
Equivalents known for the same purpose can be substituted. “In order to rely on equivalence as a rationale supporting an obviousness rejection, the equivalency must be recognized in the prior art” (MPEP 2144.06). Here, that burden is met by Fukuda et al. as they suggest anti-PD-1, specifically pembrolizumab, and anti-CTLA-4 antibodies can be interchanged in a method for treating cancer. There is a reasonable expectation of success as both pembrolizumab and anti-CTLA-4 have been used in cancer treatment, either with or without DNase, as they are both immune checkpoint inhibitors that serve the same function of blocking immune checkpoint proteins to halt cancer progression. It would be obvious to a person of ordinary skill in the art prior to the effective filing date of the instant application to substitute anti-CTLA-4 antibodies for pembrolizumab when administering in combination with DNase in a method for treating cancer since substituting one immunomodulator for another would have yielded predictable results.
Accordingly, Lee et al. in view of Fukuda et al. make obvious instant claim 12.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Lee et al as applied to claims 4 and 6-11 in view of Mittal et al. (Bharat B. Mittal, Edward Wang, Samir Sejpal, Mark Agulnik, Amit Mittal, Kirk Harris, Effect of Recombinant Human Deoxyribonuclease on Oropharyngeal Secretions in Patients With Head-and-Neck Cancers Treated With Radiochemotherapy, International Journal of Radiation Oncology*Biology*Physics, Volume 87, Issue 2, 2013, Pages 282-289.)
Lee et al. teach a method of treating a cancer in a subject in need thereof (Pg. 26, Paragraph 0072, "[a]ll of the methods described above may be used in combination… for the treatment of cancer"), comprising administering to the subject an effective amount of a deoxyribonuclease (DNase) enzyme (Pg. 25, Paragraph 0070, "DNase I") and a second immunomodulator (Pg. 25, Paragraph 0070, "anti-CTLA-4 antibody") (see claim 4).
Lee et al. do not indicate the origin of DNase I; however, DNase I can be administered to a human (Pg. 20, Paragraph 0058, "a 'subject' refers to a human or animal", Pg. 25, Paragraph 0070, "DNase I").
Mittal et al. teach administration of “recombinant human deoxyribonuclease I (rhDNase)” (Pg. 283, Introduction, second paragraph, first line) in “patients with head-and-neck (H&N) cancers” (Pg. 282, Purpose, last line). Here, rhDNase is a modified version of human DNase I; therefore, rhDNase is a species of the genus human DNase I.
Mittal et al. do not teach administration of human DNase I and an immunomodulator together.
Both human DNase I (specifically rhDNase) and immunomodulators (specifically anti-CTLA-4 antibodies) were known and used prior to the effective filing date of the application.
Thus, one of ordinary skill in the art would have found it obvious to administer DNaseI as opposed to rhDNase since they are equivalents. It is established that equivalents known for the same purpose can be substituted. “In order to rely on equivalence as a rationale supporting an obviousness rejection, the equivalency must be recognized in the prior art” (MPEP 2144.06).
Here, that burden is met because Mittal et al. teach administration of a species of human DNase I enzymes (rhDNase) and Lee et al. teach administration of DNase I, both in methods for treating cancer. There is a reasonable expectation of success in the substitution of DNase I for rhDNase as they are both endonuclease that cleave DNA used in cancer treatment. It would be obvious to a person of ordinary skill in the art prior to the effective filing date of the instant application to substitute DNase I for rhDNase in combination with an immunomodulator if the desire is to use such agent in a method for treating cancer.
Accordingly, Lee et al. in view of Mittal et al. make obvious instant claim 13.
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.
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U.S. Application No. 18/271,453
Claims 4-5 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 8 of copending Application No. 18/271,453 (reference application, hereinafter Pat. 453) as evidenced by Ireland & Oliver. Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 4 of the instant application teaches a method of treating a cancer in a subject in need thereof, comprising administering DNase enzyme and an immunomodulator. This claim is generic to the species claimed in claims 1 and 8 of Pat. ‘453, wherein the DNase enzyme is a DNase enzyme protein and the immunomodulator is at least one cell comprising a CAR or a TCR.
Claims 1 and 8 of Pat. ‘453, on the other hand, teach a method of treating a cancer in a subject in need thereof comprising administering DNase enzyme and at least one cell comprising a chimeric antigen receptor (CAR) or a T cell receptor (TCR) (claim 1 of Pat. ‘453), wherein the DNase enzyme is administered as a DNase enzyme protein (claim 8 of Pat. 453).
Therefore, Pat. 453 anticipates the claimed genus in the instant application. “[T]he species or sub-genus claimed in the conflicting patent or application anticipates the claimed genus in the application being examined and, therefore, a patent to the genus would improperly extend the right to exclude granted by a patent to the species or sub-genus should the genus issue as a patent after the species or sub-genus” (MPEP 804, part [II][B][2]).
Claim 5 of the instant application teaches that DNase is effective to reduce the number and/or activity of TAMs and/or TINs in the immunosuppressive tumor cell microenvironment.
However, “[a] chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present” (MPEP 2112.01). This function is an inherent characteristic of DNase, inseparable from its chemical structure.
“To serve as an anticipation when the reference is silent about the asserted inherent characteristic, such gap in the reference may be filled with recourse to extrinsic evidence” (MPEP 2131.01).
Ireland & Oliver teach that the administration of the DNase enzyme is effective to reduce the activity of TINs in the immunosuppressive tumor cell microenvironment (Pg. 730, Fig. 1, Legend, "Human neutrophils form neutrophil extracellular traps (NETs)… Blocking NET formation via pharmacological PAD4 inhibitors, DNAse-I, Pertussis-toxin (Ptx), or CXCR1 and −2 inhibitors allows tumor cell contact with cytotoxic immune cells"). The reduction of TIN activity by DNase would have been known by a person having ordinary skill in the art prior to the effective filing date of the application. The reference by Ireland & Oliver serves as evidence of an intrinsic property of DNase. Claim 5 is therefore included in the scope of claim 4 of the instant application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
U.S. Application No. 19/430,485
Claims 4-5 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 89 and 116 of copending Application No. 19/430,485 (reference application, hereinafter Pat. 485) as evidenced by Ireland & Oliver. Although the claims at issue are not identical, they are not patentably distinct from each other.
Claims 89 and 116 of Pat. ‘485 teach a method of treating a cancer in a subject in need thereof comprising administering DNase enzyme and antibodies against prion-like domains (PrDs) (claim 89 of Pat. 485) or a compound that inhibits expression of proteins with PrDs (claim 116 of Pat. 485).
Claim 4 of the instant application teaches a method of treating a cancer in a subject in need thereof, comprising administering DNase enzyme and an immunomodulator. This claim is generic to the species claimed in claims 89 and 116 of Pat. 485, wherein the immunomodulator is either an antibody against prion-like domains (PrDs) or a compound that inhibits expression of proteins with PrDs. Therefore, Pat. ‘485 anticipates the claimed genus in the instant application. “[T]he species or sub-genus claimed in the conflicting patent or application anticipates the claimed genus in the application being examined and, therefore, a patent to the genus would improperly extend the right to exclude granted by a patent to the species or sub-genus should the genus issue as a patent after the species or sub-genus” (MPEP 804, part [II][B][2]).
Claim 5 of the instant application teaches an intrinsic property of DNase (see above explanation with the reference by Ireland & Oliver). Claim 5 is therefore included in the scope of claim 4 of the instant application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
U.S. Application No. 19/189,164
Claims 4-7, 11-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 5, 8, and 10 of copending Application No. 19/189,164 (reference application, hereinafter Pat. 164) as evidenced by Ireland & Oliver. Although the claims at issue are not identical, they are not patentably distinct from each other.
Claims 1, 3, 5, 8, and 10 of Pat. ‘164 teach a method of treating a solid tumor in a subject in need thereof comprising administering DNase enzyme and an immunomodulator (claim 1 of Pat.164), wherein:
the immunomodulator is a checkpoint inhibitor (claim 3 of Pat. 164).
the immunomodulator comprises one of PD-1, CD28, CTLA-4, CD137, CD40, CD134 (OX-40), ICOS, KIR, LAGS, CD27, TIM-3, BTLA, GITR, TCR, 4-1BB, TIGIT, CD96, CD226, KIR2DL, VISTA, HLLA2, TLIA, DNAM-1, CEACAM1, CD155, IDO, TGF-beta, IL-10, IL-2, IL-15, CSF-1, IL-6, adenosine A2A receptor (A2AR), and a ligand thereof (claim 5 of Pat. 164).
the immunomodulator comprises one ofipilimumab, tremelimumab, nivolumab, pembrolizumab, pidilizumab, MEDI0680, atezolizumab, avelumab, durvalumab, or cemiplimab (claim 8 of Pat. 164).
the DNase enzyme comprises a human a DNase I, a human DNase-l-like 3 (D1L3), a human DNase-l-like 2 (D1L2), human DNase-l-like 1 (D1L1), a DNase X, a DNase γ, a DNase II, a DNase IIα, a DNase IIβ, and a Caspase-activated DNase (CAD) (claim 10 of Pat. 164).
Claim 4 of the instant application teaches a method of treating a cancer in a subject in need thereof, comprising administering DNase enzyme and an immunomodulator. This claim is generic to the species claimed in claim 1 of Pat. ‘164, wherein the cancer is a solid tumor.
Therefore, Pat. ‘164 anticipates the claimed genus in the instant application. “[T]he species or sub-genus claimed in the conflicting patent or application anticipates the claimed genus in the application being examined and, therefore, a patent to the genus would improperly extend the right to exclude granted by a patent to the species or sub-genus should the genus issue as a patent after the species or sub-genus” (MPEP 804, part [II][B][2]).
Claim 5 of the instant application teaches an intrinsic property of DNase (see above explanation with the reference by Ireland & Oliver). Claim 5 is therefore included in the scope of claim 4 of the instant application.
The claims of Pat. ‘164 teach the method of claim 6 from the instant application wherein the immunomodulator is an immune checkpoint modulator (claim 3 of Pat. ‘164).
The claims of Pat. ‘164 teach the method of claim 7 from the instant application wherein the immunomodulator comprises one of PD-1, CD28, CTLA-4, CD137, CD40, CD134 (OX-40), ICOS, KIR, LAGS, CD27, TIM-3, BTLA, GITR, TCR, 4-1BB, TIGIT, CD96, CD226, KIR2DL, VISTA, HLLA2, TLIA, DNAM-1, CEACAM1, CD155, IDO, TGF-beta, IL-10, IL-2, IL-15, CSF-1, IL-6, adenosine A2A receptor (A2AR), and a ligand thereof (claim 5 of Pat. 164).
The claims of Pat. ‘164 teach the method of claim 11-12 from the instant application wherein the immunomodulator comprises one of ipilimumab, tremelimumab, nivolumab, pembrolizumab, pidilizumab, MEDI0680, atezolizumab, avelumab, durvalumab, or cemiplimab OR is pembrolizumab (claim 8 of Pat. ‘164).
The claims of Pat. ‘164 teach the method of claim 13 from the instant application wherein the DNase enzyme comprises a human a DNase I, a human DNase-l-like 3 (D1L3), a human DNase-l-like 2 (D1L2), human DNase-l-like 1 (D1L1), a DNase X, a DNase γ, a DNase II, a DNase IIα, a DNase IIβ, and a Caspase-activated DNase (CAD) (claim 10 of Pat. 164).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
U.S. Application No. 19/189,161
Claims 4-5 and 13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 19/189,161 (reference application, hereinafter Pat. 161) as evidenced by Ireland & Oliver. Although the claims at issue are not identical, they are not patentably distinct from each other.
Claims 4 and 13 of the instant application teach a method of treating a cancer in a subject in need thereof comprising administering human DNase I enzyme and an immunomodulator. This claim is generic to the species claimed in claim 1 of Pat. ‘161, wherein the immunomodulator is at least one cell that expresses a CAR or a TCR.
Therefore, Pat. ‘161 anticipates the claimed genus in the instant application. “[T]he species or sub-genus claimed in the conflicting patent or application anticipates the claimed genus in the application being examined and, therefore, a patent to the genus would improperly extend the right to exclude granted by a patent to the species or sub-genus should the genus issue as a patent after the species or sub-genus” (MPEP 804, part [II][B][2]).
Claim 1 of Pat. ‘161 teach a method of treating a cancer in a subject in need thereof comprising administering DNase enzyme and at least one cell that expresses a CAR or TCR wherein said DNase comprises an amino acid sequence having at least 80% sequence identity to human DNase I enzyme.
Claim 5 of the instant application teaches an intrinsic property of DNase (see above explanation with the reference by Ireland & Oliver). Claim 5 is therefore included in the scope of claim 4 of the instant application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 4-13 are pending. Claims 4-13 are rejected. No claims are allowed.
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/J.M.P./Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642