Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on April 01, 2024. Claims 1-20 are pending and are currently examined.
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.
Claims 6, 7, 15 and 19 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 6 recites the term “intolerant” that renders the claim indefinite. It is not clear how the “intolerant” be defined. The “intolerant” is a relative term with no specific standard and a clear medical boundary. Therefore, one of ordinary skill in the art cannot determine the exact metes and bounds of the claim.
Claim 7 recites a limitation as “the subject is resistant to treatment at least two lines of previous therapy” in reference claim 1. There is insufficient antecedent basis for this limitation of “at least two lines of previous therapy” in the claim.
Claim 7 also recites terms “two lines of previous therapy”, “first-line, second-line, third-line therapies” and “beyond line” that render the claim definite. It is not clear what the “line” means.
Claim 15 recites term “in form of an injection” that render the claim indefinite. It is unclear what the form of an injection means.
Claim 19 recites a term “supportive antitumor drugs” that renders the claim indefinite. It is not clear what the “supportive antitumor drugs” means for an antitumor drug.
Accordingly, one of ordinary skill in the art will not know the metes and bounds of the claims.
Claim Rejections - 35 USC § 112 (Enablement)
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.
The base claim 1 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims. Enablement is considered in view of the Wands factors (MPEP 2164.01(a)) (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.
The base claim 1 is directed to a method for treating a subject with a central nervous system tumor, comprising: administering the subject a therapeutically effective amount of an antitumor drug, wherein the antitumor drug comprises recombinant oncolytic herpes simplex virus type II (oHSV2) with a deposit number of CGMCC No. 3600 as an active ingredient. With a deposit number of CGMCC No. 3600, it is required to practice the claimed invention. The oncolytic herpes simplex virus type II (oHSV2) must be readily available or obtainable by a repeatable method set forth in the specification, or otherwise readily available to the public. If it is not so obtainable or available, the requirements of 35 USC 112, first paragraph, may be satisfied by a deposit of the virus.
The recombinant oncolytic herpes simplex virus type II (oHSV2) disclosed in the specification does not appear to be produced from a repeatable process, and it is not apparent if the recombinant oncolytic herpes simplex virus type II (oHSV2) with an active ingredient is both known and readily available to the public. Since the claimed recombinant oncolytic herpes simplex virus type II (oHSV2) sequences are not clearly described in the specification, a deposit is required.
It is noted that Applicant has deposited the recombinant oncolytic herpes simplex virus type II (oHSV2) with a deposit number of CGMCC No. 3600 as an active ingredient, but there is no indication in the specification as to public availability.
If the deposit was made under the terms of the Budapest Treaty, then a statement, affidavit or declaration by applicants, or a statement by an attorney of record over his or her signature and registration number, or someone empowered to make such a statement, stating that all restrictions imposed by the depositor on the availability to the public of the deposited material will be irrevocably removed upon the granting of the patent, would satisfy the deposit requirement. The instant specification discloses that “the antitumor drug includes recombinant oncolytic herpes simplex virus type II (oHSV2) as active ingredient, which is named as H2d3d4-hGF, with a proposed taxonomic designation of Herpes Simplex Virus Type 2, and is deposited in depository authority of China General Microbiological Culture Collection Center located in Institute of Microbiology, Chinese Academy of Sciences, Building No. 3, Yard No. 1, West Beichen Road, Chaoyang District, Beijing, China, on February 3, 2010, with an accession number of CGMCC No. 3600 (See instant specification, page 3, paragraph 3). However, the statement in the specification regarding the restrictions must be exactly as written in the bold text above.
If the deposit was not made under the Budapest Treaty, then in order to certify that the deposit meets the criteria set forth in 37 CRF 1.801-1.809 and MPEP 2402-2411.05, applicants may provide assurance of compliance by statement, affidavit or declaration or by someone empowered to make the same or by a statement by an attorney of record over his or her signature and registration number showing that:
(a) during the pendency of the application, access to the invention will be afforded to the Commissioner upon request;
(b) all restrictions upon availability to the public will be irrevocably removed upon granting of the patent;
(c) the deposit will be maintained in a public depository for a period of 30 years or 5 years after the last request or for the enforceable life of the patent, whichever is longer;
(d) a test of the viability of the biological material at the time of deposit (see 37 CFR 1.807); and
(e) the deposit will be replaced if it should ever become inviable.
In addition, the identifying information set forth in 37 CFR 1.809(d) should be added to the specification. See 37 CFR 1.803 - 37 CFR 1.809 for additional explanation of these requirements.
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.
Claims 1-7, 9-17 and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Liu (CN102146418B, published on Jan. 15, 2014) in view of Shu et al. (CN117085049A, published on Nov. 21, 2023, hereinafter, “Shu”) and Kardani et al. (Front Cell Infect Microbiol. 2023 May 31; 13:1206111, hereinafter, “Kardani”).
The base claim 1 is directed to a method for treating a subject with a central nervous system tumor, comprising: administering the subject a therapeutically effective amount of an antitumor drug, wherein the antitumor drug comprises recombinant oncolytic herpes simplex virus type II (oHSV2) with a deposit number of CGMCC No. 3600 as an active ingredient.
Liu teaches a method for treating tumors by administrating effective recombinant oncolytic type II herpes simplex virus (oHSV2) to a patient (See Abstract; page 12, paragraph 6), where the oHSV2 was taught as “the Classification and Nomenclature of the hsv that the present invention obtains is II herpes simplex virus type, Latin name is Herpes Simplex Virus Type 2… deposit number is CGMCC No.3600” (See page 7), which teaches an identical deposition number of the recombinant oncolytic herpes simplex virus type II (oHSV2) as claimed.
However, Liu is silent on the treated tumor being a central nervous system tumor.
Shu teaches an application of oncolytic herpes simplex virus oHSV combined with BET inhibitor JQ1 in treating malignant glioma/ glioblastoma. The invention provides a new combined drug scheme for treating malignant glioma, and the oHSV recombinant virus combined JQ1 has a synergistic effect in treating malignant glioma, so that the invention has good clinical application prospect (See Abstract; Claim 1, page 1).
Kardani teaches using oncolytic herpes simplex viruses for the treatment of glioma and targeting glioblastoma stem-like cells, and discloses that present an overview of GSCs, activity of different oHSVs, clinical trial results, and combination strategies to enhance efficacy, including therapeutic arming of oHSV. Throughout, the therapeutic focus will be on GSCs and studies specifically targeting these cells. Recent clinical trials and approval of oHSV G47Δ in Japan for patients with recurrent glioma demonstrate the efficacy and promise of oHSV therapy (See Abstract).
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings from Liu, Shu and Kardani to arrive at an invention as claimed. One of skill in the art would have been motivated to do so because the oHSV recombinant virus combined JQ1 has good clinical application prospect in treating malignant glioma (See page 2) in Shu, and oHSV G47Δ can treat recurrent glioma in Kardani. There would be a reasonable expectation of success to develop a method for treating a subject with a central nervous system tumor such as glioma by administrating the oHSV2 as claimed.
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding claims 2-5, although Liu is silent on treating a central nervous system tumor, Shu teaches that the gliomas refer to tumors originating from brain glial cells, are the most common primary intracranial tumors (See page 1, Background). Shu also teaches that using oncolytic herpes simplex virus ohv in combination with BET inhibitor JQ1 for the manufacture of a medicament for the treatment of glioblastoma (See page 1, claim 4). At the same time, Kardani teaches using the G47Δ to treat recurrent glioma that is a central nervous system tumor. It would be obvious for one of ordinary skill in the art to introduce the application of oHSV2 treating glioma of Shu and kardani into the invention of Liu, and the result would be predictable to develop a method to treat a central nervous system tumor using oHSV2 as claimed. Accordingly, Liu in view of Kardani teaches claim 2 for treating a recurrent central nervous system tumor such as a recurrent glioma, and Liu in view of both Shu and Kardani teaches claim 4 for treating the glioblastoma that is a glioma in brain tumors that teaches claims 3 and 5.
Regarding claims 6-7, Liu teaches that the treatment to any particular patient depends on many factors such as patient age, body weight, sex, diet, severity, and health situation (See page 12, paragraphs 6-7), which indicates that patient can be from different condition groups. It is obvious that the patient can be from a chemotherapy and/or radiotherapy resistant group because an alternative treatment is essential to the conventional drug-resistant patients. Nevertheless, Shu teaches that temozolomide (TMZ) is the only first line drug at present to treat glioma and drug resistance has become an important reason for currently hampering treatment (See page 1), where Temozolomide (TMZ) is a chemotherapy drug can be taught by Kardani at “present standard-of-care treatment for primary GBM includes maximal safe surgical resection of the tumor, and radiotherapy with concomitant temozolomide (TMZ) chemotherapy” (See page 2, left column, paragraph 1).
Shu also teaches that gliomas act as a kind of cold tumor, and the local microenvironment is infiltrated with few immune cells, especially T cells, so the anti-PD-1 immunotherapy treatment does not achieve good efficacy in gliomas, and oncolytic Viruses (OVs) have potential anti-tumor value as a hotspot of current scientists' research (See bringing pages 1-2). Also, Kardani teaches that GBM stem-like cells (GSCs) are reported to be chemo- and radio-resistant, due to upregulation of DNA damage response proteins, and enhanced survival in vivo (See page 3, left column, paragraph 1).
Accordingly, Liu in view of Shu and Kardani teaches that the subject treated by oHSV2 can be from the patient who is intolerant to chemotherapy and/or radiotherapy as claimed. Here the description also teaches claim 7, where the resistances to the treatments of temozolomide and anti-PD-1 immunotherapy taught by Shu can be the at least two lines of previous therapy as claimed.
Regarding claim 9, Liu teaches an antitumor drug treatment using oHSV2 to Balb/c nude mice, age in 4–6-week, 16–20-gram, female by 1st day, the 4th day and the 7th day intratumor injection (See Embodiment 4, page 15). Shu teaches that a glioma treatment to 8-week-old C57BL/6 mice by intraperitoneal injection with pentobarbital, fixed in a stereotactic apparatus, and 5. Mu on days 7, 14 and 21 (See CCK8 experiment, page 3). Also, Kardani teaches that in the registration single-arm phase II trial with 19 patients with recurrent GBM, G47Δ (1x10^9 pfu in 1 ml) was stereotactically injected into 1-3 sites up to 6 times, at intervals of 5-14 days for doses 1 and 2, and 2-6 weeks for the remainder (See page 8, right column, paragraph 2).
Based on the teachings from Liu in view of Shu and Kardani, the claimed administration treatment cycle of once every 3 weeks, with administration times of ≥ 3 can vary depending the different conditions because Liu teaches that the administration time and route are depended on the patient's age, body weight, sex, diet and general health situation (See page 12, paragraph 6). Accordingly, one of skilled in the art would be able to test for an optimal treatment cycle based on the subject’s situation through routine experimentation. Thus, the claimed treatment cycle would have been obvious unless there is evidence showing that they produce unexpected results.
Regarding claims 10 and 12-14, Liu teaches a dosage of virus of the present invention is 2.5 *10^8 pfu/kg, comparative example 1 is also 2.5 *10^8 pfu/kg, where the subject is Balb/c nude mice, age in 4–6-week, 16–20-gram, female (See page 15, Embodiment 4). Liu also teaches that the virus quantity scope giving is 10^3-10^10 virus plaque forming unit (pfu), preferably 10^5-10^8 pfu, more preferably 10^6-10^8 pfu, and those skilled in the art can easily determine best route of administration and dosage based on the patient’s age, body weight and illness (See page 12). Although Liu uses the unit of “pfu” not the claimed “CCID50/ml”, Liu teaches that the dosage of administration varies depending on the condition. Thus, one of skilled in the art would be able to test for an optimal administration single dose based on the subject’s situation and needs through routine experimentation. Therefore, the claimed single dose with concentration range would have been obvious unless there is evidence showing that they produce unexpected results.
In addition, according to section 2144.05 of the MPEP, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”).
Regarding claims 11 and 15, Liu teaches an antitumor drug treatment using oHSV2 to Balb/c nude mice, age in 4–6-week, 16–20-gram, female by 1st day, the 4th day and the 7th day intratumor injection (See Embodiment 4, page 15), which indicates that the anti-tumor drug is administered as multiple doses. Also, Kardani teaches a single low dose (5 Gy) within 24 hr of oHSV inoculation, has been combined with G207 in clinical trials for adult and pediatric gliomas (See, page 13, right column, paragraph 1), and in a GSC-derived xenograft model, a single intratumoral injection of MG18L significantly extended survival by 25% and increased apoptosis in the tumor (See page 10, right column, paragraph 2). Accordingly, Liu in view of Kardani teaches claim 11. Here the “intratumor injection” teaches claim 15.
Regarding claim 16, Liu teaches that the pharmaceutical composition is injection liquid, described injection liquid comprising pharmaceutically acceptable carrier and recombinant type II herpes simplex virus vector (See e.g., page 4, item 9).
Regarding claim 17, Liu teaches that parenteral admin comprises that intravenously, intramuscular, intraperitoneal, breastbone are interior, subcutaneous, intra-articular injection and infusion (See page 12, paragraph 2), and the recombinant type II herpes simplex virus is administered to mouse by a subcutaneous injection (See page 15, Embodiment 4).
Regarding claim 19, Shu teaches an application of oncolytic herpes simplex virus oHSV combined with BET inhibitor JQ1 in the treatment of malignant glioma (Abstract), where the BET inhibitor JQ1 can inhibit glioma cell proliferation and has a synergistic treatment effect on glioma when combining using with oHSV (See page 2). It would be obvious for one of ordinary skill in the art to introduce the BET inhibitor JQ1 into Liu’s invention to arrive at an invention as claimed, and the results would be predictable based on Liu and Shu’s teachings.
Regarding claim 20, Liu teaches that the recombinant type II herpes simplex virus vector, which deletes the ICP34.5 gene and ICP47 gene of the wild type II herpes simplex virus HG52 strain, and preferably inserts hGM-CSF at the position of the deleted ICP34.5 gene expression cassette (See Abstract).
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Liu as evidenced in CenterWatch in view of Shu and Kardani as applied to claim 1-7, 9-17 and 19-20 above.
Claim 8 requires the subject is over 18 years of age.
Liu teaches that the administration route and dose are depended on patient’s age, body weight and illness (See page 12, paragraph 7), which indicates that the patient’s age can be selected based on the need that is obvious include the age 18 years and older. This can be evidenced by the CenterWatch. CenterWatch teaches that a clinical trial for investigating the safety, tolerability and efficacy of Oncolytic Virus (OVV-01) injection in the treatment of patients with advanced solid tumors has an age limitation at ≥ 18 and ≤ 70 years (See page 1). It would be obvious that one of skilled in the art can introduce the age limitation into Liu’s invention and follow the age criteria in a clinical trial.
Claim18 is rejected under 35 U.S.C. 103 as being unpatentable over Liu in view of Shu and Kardani as applied to claims 1-7, 9-17 and 19-20 above and further in view of Peyrl et al. (J Neurooncol. 2014 Oct;120(1):139-45).
Claim 18 requires that the ommaya reservoir is used as a device for administering the antitumor drug into the subject.
Based on the description above, Liu teaches administering the antitumor drug into the subject, however, it is silent on the Ommaya reservoir.
Peyrl teaches that the Ommaya reservoir facilitates repetitive delivery of drugs into the CSF and is a pharmacologically rational system for intrathecal chemotherapy and discloses that Ommaya reservoirs are a safe and convenient means for delivering chemotherapy in children with brain tumors, and provides a reliable and well tolerated means for repeated intraventricular drug delivery even in infants and young children (See page 144, left column, paragraph 2; page 142, right column).
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to introduce the Ommaya reservoir into Liu’s invention to arrive at an invention as claimed. One of skill in the art would have been motivated to do so to use Ommaya reservoirs for repeated intraventricular drug delivery. There would be a reasonable expectation of success to develop a method using Ommaya reservoirs as claimed.
Conclusion
No claims are allowed.
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/RUIXUE WANG/ Examiner, Art Unit 1672
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