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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06/19/2025 has been entered.
Priority
This application was filed on October 19, 2020, and is a 371 application of PCT/EP2019/061122 filed on April 30, 2019, which claims benefit to the foreign application GB1807050.8 filed on April 30, 2018.
Claim Status
In the response, filed June 19, 2025, Applicant has amended claims 3 and 29 and cancelled claims 1-2, 4, 8, 10-11, 13, 15-17, 19, 21, 23, 25-28, 32-34, 36, and 40.
Currently, Claims 37-39 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on October 27, 2023.
Currently, claims 3, 5-7, 9, 12, 14, 18, 20, 22, 24, 29-31, and 35 are under examination.
Withdrawn Objections & Rejections
Rejections and/or objections not reiterated from the previous office action are hereby withdrawn due to amendment. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. Thus, the objections and rejections presented herein represent the full set of objections and rejections currently pending in the application. Any objections or rejections not specifically reiterated are hereby withdrawn.
Claim Rejections - 35 USC § 112
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.
Claims 3-7, 9, 12, 14, 18, 20, 22, 24, 29-31, and 35 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Independent claims 3 and 29 recite administering an anti-herpes viral agent to the patient with the natural killer (NK) cells and/or NK-like T cell therapy. However, the specification doesn't have adequate support in the disclosure for a generic anti-herpes viral agent that characterize any anti-herpes viral agent with NK cell and/or NK-like T cell therapy that is administered to a patient treat herpes virus reactivation. As written in the claim, “anti-herpes viral agent” encompasses a broad genus that includes multiple classes of inhibitors, and given its broadest reasonable interpretation in light of the specification (i.e. vaccines, nucleoside analogue, active metabolite, prodrug, salt, solvate or hydrate of such nucleoside analogues etc.), corresponding to any anti-herpes viral agent that imparts the function of anti-herpes viral activity.
Dependent claims 22 and 35 recite wherein the anti-herpes viral agent comprises a nucleoside analogue, optionally selected from the group consisting of: valacyclovir; acyclovir; famciclovir; and/or penciclovir, or an active metabolite, prodrug, salt, solvate or hydrate of such nucleoside analogues. In the instant case, this claim limitation does not remedy the issue because this claim limitation is directed to any nucleoside analogue. Thus, the specification doesn't have adequate support in the disclosure for a generic nucleoside analogues that is administered to a patient treat herpes virus reactivation. As written in the claim, “nucleoside analogue” encompasses a broad genus that includes many nucleoside analogues and given its broadest reasonable interpretation in light of the specification (i.e. any prodrug, salt, solvate or hydrate of such nucleoside analogues etc.), corresponding to any anti-herpes viral agent that imparts the function of anti-herpes viral activity.
Under the written description guidelines (see MPEP 2163), the Examiner is directed to determine whether one skilled in the art would recognize that the Applicant was in possession of the claimed invention as a whole at the time of filing. The following considerations are critical to this determination.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail so that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result, but the disclosure fails to sufficiently identify how the function is performed, or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. "Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement." Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).
Accordingly, to satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.
In analyzing whether the written description requirement is met for genus, “anti-herpes viral agent”, the specification is first assessed to determine whether a representative number of species have been described by their complete structure of the genus.
Independent Claim 3 and 29 recites administering an anti-herpes viral agent to the patient with the NK cell and/or NK-like T cell therapy. However, the specification doesn't have adequate support in the disclosure for a generic anti-herpes viral agent that characterizes any anti-herpes viral agent with natural killer cells administered to a patient treat herpes virus reactivation.
Dependent claims 22 and 35 recite wherein the anti-herpes viral agent comprises a nucleoside analogue. However, the specification doesn’t have adequate support in the disclosure for a structure of a generic nucleoside analogue that characterizes any nucleoside analogue with natural killer cells that is administered to a patient to treat herpes virus reactivation.
The specification only discloses “Acyclovir and penciclovir are both guanosine analogues that inhibit viral replication by acting as a substrate for viral DNA polymerase. Valacyclovir is a prodrug, an esterified version of acyclovir that has greater oral bioavailability” (Specification, page 17). Although the specification discloses that the anti-herpes viral agent could be known anti-herpes viral agent including other nucleoside analogues with anti-viral activity may be identified by standard methods known in the art (see e.g. para. 91), but the specification does not describe the structure of all nucleoside analogues that inhibit viral replication. Therefore, the specification fails to identify any anti-herpes viral agent and any nucleoside analogue that when administered with natural killer cells to a patient treats herpes virus reactivation.
The method of making the claimed invention is not well established at the time of filling. However, one of skill in the art would neither expect nor predict the appropriate method of treating herpes virus reactivation in a patient by administering natural killer cells with an anti-herpes viral agent as claimed using any anti-herpes antiviral agent with natural killer cells.
The teaching of Irwin et al. (Virus evolution 2.1, published 2016), indicates that for the herpesvirus (HSV) the “systemic antiviral therapy is usually only necessary in immune-compromised patients, where it is relatively successful. The most commonly used drugs are Acyclovir and its related analogs, all nucleoside inhibitors, for which resistance mutations are known, affecting either a thymidine kinase necessary for prodrug activation by phosphorylation or the DNA polymerase” (page 3, col. 1-2 of Irwin et al.). Therefore, Irwin et al., provides robust evidence that specific anti-herpes viral agents, such as Acyclovir and its related analogs, are used for anti-viral therapy of HSV, and they are associated with relatively successful treatment.
Additionally, Martinez et al. (Natural product reports 32.1: 29-48, published 2015), teaches that there is an “arsenal of anti-virals that are complex and consists of (i) directly acting antivirals (DAAs), i.e. drugs that directly affect virus-derived components including viral proteins and viral genomes and (ii) host acting antivirals (HAAs), i.e. modifiers of host factors or host pathways that affect virus life cycles as well as immune response components or immune response modifiers including antibodies, interferons and vaccines” (page 2, see section 1.2 of Martinez et al.). Therefore, Martinez et al. provides additional evidence that there are many types of antiviral agents that are complex (see Figure 2 and Table 2 of Martinez et al.); however, Martinez et al does not teach that any anti-viral agent with natural killer cells is able to treat herpes virus reactivation in a patient.
Therefore, with these additional evidence, the ordinary artisan cannot predictably identify that any anti-herpes viral agent with the administration of natural killer cells will treat herpes virus reactivation in a patient.
Furthermore, the functionally defined genus claims can be inherently vulnerable for lack of adequate written description, especially in highly unpredictable technology fields, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. See ABBVIE DEUTSCHLAND GMBH & 2 CO. v. JANSSEN BIOTECH, INC., Appeals from the United States District Court for the District of Massachusetts in Nos. 09-CV-11340-FDS, 10-CV-40003-FDS, and 10-CV-40004-FDS, Judge F. Dennis Saylor, IV. See also Ariad, 598 F.3d at 1351 ("[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology.”); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein).
The Applicant has recited that “the following anti-viral agents are all analogues of acyclic guanosine and are commercially available: Zovirax® (acyclovir), Valtrex® (valacyclovir), Denavir® (penciclovir), and Famvir® (famciclovir). Other nucleoside analogues with anti-viral activity are known in the art and may be used in the context of the present invention. For example, Bromovinyl deoxyuridine (Brivudin) is a highly potent thymidine nucleoside analogue with selective activity against HSV-1 and VZV. It is understood that bicyclic pyrimidine nucleoside analogues (BCNAs) have anti-viral activity” (Specification, page 17-18). Given the breadth of any “anti-viral agent” that the claims embrace, a description of one species, analogues of acyclic guanosine, fails to provide a representative number of species that teaches the complete structure of the genus of any anti-herpes viral agent. Consequently, any anti-herpes viral agent is not apparent to one of ordinary skill in the art from the description present in the specification. Therefore, an artisan of ordinary skill could not envision all the embodiments encompassed by the breadth of the claims.
Accordingly, the specification doesn't have adequate support in the disclosure for a generic anti-herpes viral agent that can characterize any anti-herpes viral agent with the administration of natural killer cells will treat herpes virus reactivation in a patient. Similarly, disclosure doesn't identify a generic anti-herpes viral agent that characterizes any anti-herpes viral agent with the administration of natural killer cells will treat herpes virus reactivation in a patient. Therefore, the claimed recitation of any anti-herpes viral agent doesn't have an adequate written description. Furthermore, neither the specification nor the art indicates the ability to identify generic anti-herpes viral agent that characterizes any anti-herpes viral agent with the administration of natural killer cells will treat herpes virus reactivation in a patient.
Therefore, it concludes that the claimed recitation of any anti-herpes viral with the administration of natural killer cells will treat herpes virus reactivation in a patient doesn't have an adequate written description. Specifically, the specification does not identify the generic anti-herpes viral agents to characterize any anti-herpes viral agent that can be administered with natural killer cells that will treat herpes virus reactivation in a patient. It concludes that a skilled artisan would find the specification inadequately described. Therefore, the Applicant did not sufficiently possess the broader invention as claimed.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 3, 5-7, 9, 12, 14, 18, 20, 22, 24, 29-31, and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Kang et al. (US20180021378A1, application no. 15/541,006; published Jan. 25, 2018; cited IDS 3/9/2021, prior art of record), Fukushima, Toshihiro, et al. (Anticancer research 32.12: 5437-5440, published 2012), Vickrey, Eric, et al. (Cancer 115.1: 229-232, published 2009, cited IDS 3/9/2021), Schaffer et al. (US2009/0176743 A1, published 2009, cited IDS 3/9/2021; prior art of record), Evren Alici (US8877182B2, published 2014), and Peled et al. (U.S. application US2013/0011376A1, published 2013, prior art of record).
This rejection is a new rejection necessitated by amendments to the claims. However, since it is similar to a rejection set forth in the non-final Official action mailed on Feb. 21, 2025, therefore any aspect of applicant's response considered relevant to the rejection as newly set forth is responded to following the statement of rejection.
Regarding claim 3, 9, 5-7, 12, 22, 29-30, and 35, Kang discloses methods for treating infectious disease (i.e. herpes virus) or malignant disease (i.e. myeloma) in a patient (see e.g. abstract), wherein the patient has received a therapy comprising natural killer (NK) cells (see e.g. abstract, claims 1, 66, and 148, paras. 7, 93, 148, 189, 469-472). Kang discloses wherein the method comprises the step of administering an anti-herpes viral agent (i.e. valaciclovir or valacyclovir) to the patient with the NK-cell therapy (see e.g. claims 37-40). Kang teaches that the anti-viral agent can be administered before, after, or at the same time as the NK cells (see e.g. para. 509), corresponding to the claim limitation wherein the anti-herpes viral agent is administered before and/or concurrently and/or after the patient has received the NK cell and/or NK-like T cell therapy. Further, Kang teaches that NK cells or the agent can be administered once every 1, 2, 3, 4, 5, 6 or 7 days during therapy (para. 509). Further, Kang teaches that the NK cells or the anti-viral agent can be administered without regard to whether the NK cell or the anti-viral agent have been administered to the individual in the past. Thus, Kang teaching that the NK cells or anti-viral agent can be administered once every 2 days (para. 509) reads on the claim patient receiving the anti-viral agent at least one day before receiving NK cells. Further, Kang teaches natural killer cells can be isolated using, e.g., antibodies to CD3 and CD56, and by selecting for cells that are CD56+ to produce a first cell population, and contacting said first cell population with antibodies specific for CD3 (see e.g. para. 238 and 243). Further, Kang discloses wherein the NK cells have been expanded and have the phenotype CD3-CD56+ (para. 73, 75, 105-106, 112-117, 127, claim 144, 146).
Kang does not explicitly state wherein the NK-like T cells have the phenotype CD3+CD56+, wherein the method is suppressing and/or reducing a herpes virus reactivation in a patient, or wherein NK cell therapy induces herpes virus reactivation.
However, the prior art of Alici discloses obtaining ex vivo expanded and activated natural killer (NK) cells with the phenotype CD3+CD56+ and the phenotype CD3−CD56+ (see e.g. abstract, and Examples).
Accordingly, it would have been obvious for a person of ordinary skill in the art to modify the NK cell therapy method (as taught by Kang) with NK-like T cells that having the phenotype CD3+CD56+ (as taught by Alici) because Alici discloses that the NK cells and NK-like T cells exhibit an increased cytotoxicity with CD3+CD56+ or CD3-CD56+ (see e.g. abstract, fig. 2, example 3). A person of ordinary skill in the art would have had predictable results with a reasonable expectation of success because Kang and Alici both disclose that the methods for obtaining the NK cell and NK-like T cell phenotype CD3 and CD56 were well known in the art (see e.g. abstracts, respectively). Further, Alici discloses that expanded cells with the phenotype of with CD3+CD56+ or CD3-CD56+ exhibited increased cytotoxicity (see e.g. claim 1 and summary). Thus, providing motivation to do.
As stated above, Kang does not explicitly state wherein the method is suppressing and/or reducing a herpes virus reactivation in a patient.
However, the prior art of Fukushima discloses that the anti-herpes viral agent (i.e. valaciclovir or valacyclovir) is effective in suppressing and/or reducing a herpes virus reactivation in patients with myeloma (see e.g. abstract, page 5437-5440).
Accordingly, it would have been obvious for a person of ordinary skill in the art to modify the method for treating infectious disease (i.e. herpes virus) or malignant disease (i.e. myeloma) in a patient (see e.g. abstract) as taught by Kang with treating reactivation of a herpes virus as taught by Fukushima because Fukushima discloses that patients with myeloma, are at a significant risk of herpes virus reactivation (see e.g. abstract). Further, Kang discloses that the NK cells are administered to the subject having a viral infection as part of an antiviral therapy regimen that includes one or more other antiviral agents (e.g. protease inhibitor). A person of ordinary skill in the art would have had a reasonable expectation of success because both Kang and Fukushima disclose using anti-viral agents to treat herpes virus. Additionally, the prior art of Vickrey discloses that it is clinical practice to a administer anti-herpes viral agent (i.e. acyclovir) long-term to all symptomatic myeloma patients irrespective of the therapy they are receiving (see e.g. page 230). Thus, a person of ordinary skill in the art would have had predictable results a reasonable expectation of success Moreover, an artisan of ordinary skill in the art of (NK cell and/or NK-like T cell therapy) has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007).
As stated above, Kang does not explicitly state wherein NK cell therapy induces herpes virus reactivation.
However, the prior art of Schaffer discloses administering NK cell therapy and an anti-herpes viral agent to treat reactivation of a latent herpes infection (see e.g. para. 16, 34, 139-141).
Furthermore, the MPEP 2111.04 states “The broadest reasonable interpretation of a method (or process) claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent is not met.” In the instant case, the claim recites “wherein the NK cell and/or NK-like T cell therapy induces and/or increases herpes virus reactivation” (claim 3, line 7-8). Therefore, the method of Kang disclosing a patient receiving NK cell therapy would naturally induce and/or increase herpes virus reactivation.
Accordingly, it would have been obvious to one of ordinary skill in the art to have the method of Kang with an induced and/or increase of herpes virus reactivation (as taught by Kang and Schaffer) because Kang teaches administering NK cell therapy to a patient with an infectious disease (i.e. herpes virus) and malignant disease (i.e. myeloma)(see e.g. abstract, claims 1, 66, and 148, paras. 7, 93, 148, 189, 469-472). Furthermore, the prior art of Schaffer discloses administering NK cell therapy and an anti-herpes viral agent to treat reactivation of a latent herpes infection (see e.g. para. 16, 34, 139-141). Thus, a person of ordinary skill in the art would have had predictable results with a reasonable expectation of success.
Regarding claims 3, 9, and 29, Kang teaches natural killer cells can be isolated using, e.g., antibodies to CD3 and CD56, and by selecting for cells that are CD56+ to produce a first cell population; contacting said first cell population with antibodies specific for CD3 (see e.g. para. 238 and 243). Further, Kang discloses wherein the NK cells have been expanded and have the phenotype CD3-CD56+ (para. 73, 75, 105-106, 112-117, 127, claim 144, 146).
Kang does not explicitly state the NK-like T cells have the phenotype CD3+CD56+ or CD3-CD56+ and have been expanded ex vivo.
However, the prior art of Alici discloses obtaining ex vivo expanded and activated natural killer (NK) cells with the phenotype CD3−CD56+ and NK-like T cells with the phenotype CD3+CD56+ (see e.g. abstract, and Examples).
Accordingly, it would have been obvious for a person of ordinary skill in the art to modify the NK cell therapy method (as taught by Kang) with NK-like T cells that having the phenotype CD3+CD56+ or CD3-CD56+ (as taught by Alici) because Alici discloses that the NK cells and NK-like T cells exhibit an increased cytotoxicity (see e.g. abstract, fig. 2, example 3). A person of ordinary skill in the art would have had predictable results with a reasonable expectation of success because Kang and Alici both discloses that the method for obtaining the NK cell and NK-like T cell phenotype CD3+CD56+ or CD3-CD56+ were well known in the art (see e.g. abstracts, respectively). Further, Alici discloses that expanded cells exhibited increased cytotoxicity (see e.g. claim 1 and summary).Thus, providing motivation to do.
Regarding claim 14, Kang does not explicitly state the dosage of the anti-herpes viral agent.
However, the prior art of Fukushima discloses wherein 500mg of that the anti-herpes viral agent (i.e. valaciclovir or valacyclovir) is administered within a 24 hour period (i.e. daily) (see e.g. page 5438) for at least one month (see e.g. abstract, table 1, page 5439). Further, the prior art of Schaffer teaches that the anti-viral agent (i.e. valaciclovir or valacyclovir) can be administered one to four times daily (i.e. 24 hours) in the amount of 1 to 1000 mg per unit dose (see e.g. para. 130), corresponding to the claim limitation of 500-1000mg of the anti-viral agent is delivered to the patient within a 24 hour period.
Accordingly, it would have been obvious for a person of ordinary skill in the art to modify the NK cell therapy method (as taught by Kang) with the administration of the anti-herpes viral agent as taught by Fukushima and Schaffer because Fukushima discloses that500 mg daily of Valacyclovir at a dose of 500 mg daily appears to be effective at preventing herpes reactivation (see e.g. abstract). Further, a person would have had a predictable results with a reasonable expectation of success because Kang, Fukushima, and Shaffer disclose administering the anti-herpes viral agent (see e.g. respective abstracts). Further, Kang teaches that using natural killer cells in combination with a second agent (i.e. anti-herpes viral agent e.g. valaciclovir or valacyclovir) allow for target specificity and/or homing specificity (abstract). Thus, providing motivation to do.
Regarding claim 18 and 31, Kang et al discloses wherein the individual has received a bone marrow transplant before said administering of natural killer (NK) cells (para 461). Further, the prior art of Fukushima discloses patients with Myeloma undergoing hematopoietic stem cell collection (see e.g. page 5438).
Kang is silent regarding an autologous stem cell transplantation (ASCT).
However, the prior art of Peled discloses wherein the patient receives NK cell and/or NK-like T cell therapy following autologous stem cell transplantation (ASCT) (para, 8, 17, 143 and 285). Additionally, the prior art of Vickrey discloses that it was known in the prior art for myeloma patients to undergo autologous hematopoietic stem cell transplantation (HSCT) with high-dose therapy prevent herpes simplex virus reactivation (see e.g. page 230).
Accordingly, it would have been obvious for a person of ordinary skill in the art to modify the NK cell therapy method (as taught by Kang) with the administration of the anti-herpes viral agent to a patient that has received autologous stem cell transplantation (ASCT) (as taught by Peled and Vickrey) because Vickrey discloses that is was a known for malignant diseases patients to undergo autologous hematopoietic stem cell transplantation (HSCT) (see e.g. page 230). Thus, it would have been obvious for a person of ordinary skill in the art to have had predictable results with a reasonable expectation of success. Moreover, an artisan of ordinary skill in the art of (NK cell and/or NK-like T cell therapy) has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007).
Regarding claim 20, Kang discloses NK cell therapy comprises one or more administration of the NK cells (see e.g. claim 62-63). Kang discloses the anti-herpes viral agent (i.e. second agent) is administered intravenously, subcutaneously and/or intramuscularly (see e.g. claim 25, 27, para. 489). Further, Kang teaches administering at least 5 X 106 NK cells (para. 146, 160, 184, 343, and 504) to an individual.
Although Kang et al is silent regarding the amount of 5X106 cells/kg body weight of the patient.
Nevertheless, it would have been obvious to use the same number of cells based on the body weight of the patient as taught by Schaffer which teaches that dosing is partly determined by body weight (para. 146).
In regards to overlapping ranges, MPEP 2144.05(I) states, “In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”, continuing in regards to ranges are close, “Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)”.
In regards to routine optimization, MPEP 2144.05(II)(A) states, “generally differences in concentration 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); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (‘It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.’)”.
Accordingly, it would have been obvious for a person of ordinary skill in the art to modify the NK cell therapy method (as taught by Kang) with the patient’s body weight as taught Schaffer because Schaffer discloses that dosing is partly determined by body weight (para. 146). Thus, it would have been obvious for a person of ordinary skill in the art to optimize the amount of dosage that is administered based on the patient’s body weight. Further, Kang et al teaches using natural killer cells at various concentration (para. 343-343). Therefore, a person of ordinary skill in the arts could have arrived at these concentrations with a reasonable expectation of success. Moreover, an artisan of ordinary skill in the art of (NK cell and/or NK-like T cell therapy) has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007).
Regarding claim 24, as discussed supra, Kang discloses administered for treating reactivation of herpes viral infections or the diseases or conditions caused therewith, including conditions caused by varicella zoster virus (VSV), Herpes simplex virus (HSV1), cytomegalovirus (CMV), Epstein Barr virus (EBV), as well as shingles virus (see e.g. para. 484).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Response to Traversal:
Applicant argues that the prior art of record does not teach that NK cell and/or NK-like T cell therapy induces herpes virus reactivation (Remarks, page 9). Applicant asserts that the prior art fails to teach or suggest the induction of herpes virus reactivation (Remarks, page 9-10).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
It is noted that the test for obviousness is not whether the features of a secondary reference maybe bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413,208 USPQ 871 (CCPA 1981). The MPEP 2123 (I) states that patents are relevant as prior art for all they contain, and that a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments.
In instant case, the NK cell and/or NK-like T cell therapy and anti-herpes viral agent as taught by Kang et al., Fukushima, Toshihiro, et al., Vickrey, and Schaffer et al., disclose the anti-herpes viral agents (i.e. valaciclovir or valacyclovir) found in the cell therapy art (see e.g. Kang para. 487) and appear both in the specification and in the claims. Furthermore, the prior art of Kang discloses the viral infection of shingles (i.e. herpes virus reactivation)(see e.g. para. 484). Furthermore, the prior art of Fukushima discloses that administering anti-herpes viral agents (i.e. valaciclovir or valacyclovir) were known to suppress or reduce herpes virus reactivation (see whole document). In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Applicant argues that Kang et al., and Schaffer et al., only describe anti-viral agents for treating an infectious disease, such as a viral infection, once the patient already has the disease (Remarks, page 10). Applicant argues that the skilled person who observes herpes virus following NK cell therapy would only be able to treat the herpes virus and not prevent herpes virus reactivation because a skilled person could not know from the prior art that a patient who received NK cell therapy would go on to develop shingles – that was only discovered by the present inventors (Remarks, page 10-11).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
In response to Applicants argument regarding Kang et al., and Schaffer et al., the prior art of Kang recites the viral infection of shingles (see e.g. para. 484), and the prior art of Schaffer recites “preventing reactivation of a latent herpesvirus infection” (see e.g. abstract). Further, the Kang discloses that the antiviral agents that may be administered to an individual having a viral infection like shingles (i.e. herpes reactivation)(see e.g. para. 487). Additionally, the prior art of Vickrey discloses that it was well known that immunocompromised patients are at risk of developing herpes zoster (see e.g. abstract). Therefore, it is unclear how a person of ordinary skill in the art would not know how to treat a patient that developed herpes virus reactivation (i.e. shingles) when both Kang and Schaffer literally discloses treating patients with a herpes virus reactivation (i.e. shingles).
Furthermore, the MPEP 2111.04 states “The broadest reasonable interpretation of a method (or process) claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent is not met.” In the instant case, the claim recites “wherein the NK cell and/or NK-like T cell therapy induces and/or increases herpes virus reactivation” (claim 3, line 7-8). As discussed above, the method of Kang disclosing a patient receiving NK cell therapy and a herpes antiviral agent (i.e. Valaciclovir), which would then naturally induce and/or increase herpes virus reactivation absent evidence to the contrary. In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Applicant asserts that the prior art of Peled is cited for teaching the NK-like cells can have the phenotype CD3+CD56+ and do not teach or suggest that NK cell and/or NK-like T cell therapy induces herpes virus reactivation (Remarks, page 11).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
In response to Applicants argument the prior art of Peled is no longer cited for teaching NK-like cells can have the phenotype CD3+CD56+ . As discussed above, the prior art of Kang discloses that natural killer cells can be isolated using, e.g., antibodies to CD3 and CD56, and wherein the NK cells have been expanded and have the phenotype CD3-CD56+ (para. 73, 75, 105-106, 112-117, 127, claim 144, 146). Further, the prior art of the prior art of Alici is cited for teaching obtaining ex vivo expanded and activated natural killer (NK) cells with the phenotype CD3−CD56+ and NK-like T cells with the phenotype CD3+CD56+ (see e.g. abstract, and Examples) because they have increased cytotoxicity (see e.g. abstract). Thus, it would have been obvious for a person of ordinary skill in the art to modify the methods of Kang with the NK-like T cells of Alici to obtain cells with increased cytotoxicity.
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Conclusion
No claim is allowed.
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/JOSEPHINE GONZALES/ Examiner, Art Unit 1631
/JAMES D SCHULTZ/ Supervisory Patent Examiner, Art Unit 1631