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 .
Election/Restrictions
Applicant’s election of the species “wound healing” in the reply filed on 7/29/26 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 11 and 13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7/29/26.
Claim Status
Claim 14 is cancelled.
Claims 1-13 and 15-24 are pending.
Claims 11 and 13 are withdrawn.
Claims 1-10, 12 and 15-24 are presented for examination on the merits as they read upon the elected subject matter.
Priority
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Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/14/23 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claims 15-24 are objected to because of the following informalities: the claims do not end in a period “.”. See MPEP 608.01(m): “Each claim begins with a capital letter and ends with a period.”
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 15-24 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. Claims 15-24 contain parenthetical expressions “(cm)” “(s/cm2)” “(hours)” “(°C)” and “(m/s)”. Parenthetical expressions are not permissible which do not contribute to clearness or exactness in stating Applicant’s invention (Ex parte Cahill, 1893 C. D., 78; 63 O. G., 2125). These claims contain parentheses which raises the question as to which term is required by the claim because the subject matter in the parentheses is not identical in scope. Essentially, the claims use both narrow “(cm)” “(s/cm2)” “(hours)” “(°C)” and “(m/s)” and broad limitations of distance, time, temperature and velocity. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
Claim Rejections - 35 USC § 102
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.
Claim(s) 1, 3-6, 8 and 12 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shekhter et al. (Nitric Oxide 2005;12:210-219).
Regarding claims 1, 8 and 12, Shekhter et al. disclose methods of treating skin wounds with gaseous nitric oxide at a dose of 500 ppm generated by air-plasma unit “Plason”, which generates NO from the atmosphere air by the plasmo-chemical reaction promoted by the high plasma temperature of an electric arc discharge (Page 211, left column), to improve healing of skin wounds in rats (Title; Abstract). The dose of 500 ppm falls within the claimed range of about 200 to 1000 ppm and anticipates the claimed range. See MPEP 2131.03(I): A SPECIFIC EXAMPLE IN THE PRIOR ART WHICH IS WITHIN A CLAIMED RANGE ANTICIPATES THE RANGE.
Shekhter et al. state: “the gaseous NO flow is directed towards intact skin above the animal abdomen for 30 s” (Page 217, Figure 9). Shekhter et al. also observed: “We showed that endogenous NO is responsible for the formation of these complexes, and that this NO is synthesized by NOS enzymes. The EPR experiments gave direct proof that gaseous NO treatment increased the stationary level of endogenous NO molecules in the wound tissues… We have established beyond doubt that the beneficial effects of the gas treatment gaseous NO are accompanied by enhanced NO levels in the wound tissue. By implication, more endogenous NO molecules become available as signalling molecules to regulate the metabolic processes in wound tissue.” (Page 218, left column 1st paragraph). Thus, a therapeutic benefit of stimulating sub-dermal production of NO was achieved as well as mobilization of NO generated by a plasma source across and through the dermis, and the direct effect of NO in combination with other chemical and physical components of the plasma stream, including UV radiation and heat flow inherently produced by the plasma source, on pathogens. Shekhter et al. report that: “The gas flow treatment shortened the recovery time of both aseptic and purulent wounds (300 mm2 area) by nearly a third. The treatment allows to achieve a marked improvement in the histological, histochemical, and electron-microscopic characteristics of the affected tissue.” (Abstract).
Regarding claims 1 and 3-5, Shekhter et al. disclose that the animals with infected wounds (Staphlococcus aureus) were exposed to NO-containing gas flow on the second, third, fourth and sixth days for 60 seconds (Page 212, upper left column). Thus, there were 4 applications, which falls within the claimed range of from 1 to 24 discrete applications and the multiple discrete applications were separated by 24 hours and 48 hours, which falls within the claimed time period of from 3 to 168 hours. Shekhter et al. state: “the air-plasma unit "Plason" has been used to treat more than 10,000 patients with a wide variety of skin wounds and other disorders The patient group included individuals with complicated, protracted postoperative wounds, purulent and gunshot wounds, burns, and trophic ulcers associated with venous insufficiency, atherosclerosis, diabetes mellitus, radiation therapy, bedsores, necroses of the skin grafts, osteomyelitis, etc. The gas treatment markedly accelerated the healing process throughout this group” (Page 218, left column 2nd paragraph).
Regarding claim 6, Shekhter et al. discloses: “After leaving the plasma chamber, the NO-containing gas flow is cooled to 18-20 °C. The NO content of the gas flow can be controlled in the range between 0 and 2500 ppm. In this work, the NO levels of the gas flow were set to 800-1000 ppm… The dependence of NO content in gas flow from the distance from outlet of the manipulator is shown in Fig. 2.” (Page 211, left column last paragraph and Figure 2). It is the Examiner’s position that the temperature range employed by Shekhter et al. anticipates the claimed range because these were the measured experimental temperatures.
Claim(s) 1, 2, 4-10, 12 and 15-24 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nelson et al. (US20160193336).
Regarding claims 1-2, Nelson et al. disclose in claims 1-2:
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The same plasma state discrete stream of matter inherently has NO as the most prominent component together with other chemical and physical components including UV radiation and heat flow produced by the plasma stream. See also claims 31-32. Once a prima facie case of anticipation has been established, the burden shifts to the Applicants to prove that the prior art product does not necessarily or inherently possess the characteristics of the claimed product. See In re Best, 562 F.2d 1252, 1255 (CCPA 1977).
Regarding claims 4-10, Nelson et al. disclose:
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Regarding claim 12, Nelson et al. disclose wound healing (Claim 13).
Regarding claims 15-24, Nelson et al. disclose:
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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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1-10, 12 and 15-24 are rejected under 35 U.S.C. 103 as being unpatentable over Nelson et al. (US20180228836) and Miller (US20070065473) and Shekhter et al. (Nitric Oxide 2005;12:210-219).
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103, the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103.
Applicant claims:
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Claim interpretation: the limitation of “other chemical and physical components of the plasma stream” are comprising “UV radiation and heat flow”.
Level of Ordinary Skill in the Art
(MPEP 2141.03)
MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). The level of skill is that of a therapeutic nitric oxide research scientist, as is the case here, then one can assume comfortably that such an educated artisan will draw conventional ideas from the application of therapeutic nitric oxide techniques and materials— without being told to do so.
In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(II)).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Regarding claims 1 and 12, Nelson et al. teach methods for administering nitric oxide in a plasma state to a treatment site where a direct stream of matter is directed at a site of action to achieve a therapeutic result (Abstract) where the site of action can be open wounds [0028] and trauma/wounds/inflammation [0050]. Thus, the therapeutic result would be wound healing and at least “open wounds” infers dermal skin wounds where the stream of gas at a site of action to obtain a therapeutic result by at least one of stimulating sub-dermal production of NO, mobilization of NO generated by a plasma source across and through the dermis, and the direct effect of NO in combination with other chemical and physical components of the plasma stream, including UV radiation and heat flow, on pathogens. UV radiation and heat flow would be a natural result from the use of plasma arc discharge. (See the instant specification [0019]). Nelson et al. teach that nitric oxide is the most prominent therapeutic component together with other chemical and physical components ([0012, 0100]; Claims 2 and 13). Nelson et al. provide in [0111]: “Referring now to FIG. 4, a flow diagram illustrating an exemplary method for administering NO in a plasma state to a treatment site in accordance with the present disclosure is shown. At a first step 100 of the exemplary method, a discrete stream of matter that has been put into a state of plasma may be created, in which the stream has, as part of its content, NO in a concentration from about 5 ppm to 3500 ppm.” A range of about 5-3500 ppm overlaps the claimed range of about 200 ppm to 1000 ppm. MPEP 2144.05(I): 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). Nelson et al. teach in Example 3 [0107]:
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Regarding claim 2, as shown in Table 3, the distance to the site is between 1 and 45 cm which overlaps the claimed range of from 1-25 cm.
Regarding claim 3, as shown in Table 3, the time of application is from 1 to 45 sec/cm2 which overlaps the claimed range of for 5 to 60 s/cm2.
Regarding claim 4, as shown in Table 3, the number of treatments is from 1 to 200 which overlaps the plurality of discrete application of from 1 to 24.
Regarding claim 5, as shown in Table 3, the time periods are separated by 3 to 168 hours.
Regarding claim 6, as shown in Table 3, the temperature is from 10-60 degrees C.
Regarding claim 7, as shown in Table 3, the velocity is from 0.05 to 200 m/s, which overlaps the claimed range.
Regarding claims 8-10, Nelson et al. teach using an electric acid discharge device (Claim 5 and 16), a microwave discharge device (Claims 6 and 17) or a gliding arc discharge device (Claims 7 and 18).
Regarding claims 15-24, the claimed parameters all fall within the scope of the parameters provided by Nelson et al. in Table 3 above. Nelson et al. explain the meaning of the parameter in [0103] and provide other Tables of treatment schemes (Tables 1-6). Thus, these parameters are result-effective variables routinely optimized by the artisan to achieve their desired effect. See MPEP 2145.05 II(B) and III(C).
Regarding claims 1 and 12, Miller teaches methods for treating injured mammalian tissues with an effective amount of exogenous gaseous nitric oxide (gNO), which would be the most prominent component, in order to promote healing by reducing the size, duration and severity of wounds as well as controlling the infection by reducing number of pathogens at the site and the surrounding area (Abstract) with about 20-1000 ppm gaseous nitric oxide applied to the skin (Claims 1, 7, 12-13 and 17). The therapeutic result of wound healing is observed in the wounds treated with gNO [0181]. Since the amount of gaseous NO is the same as claimed and directed at the skin, thus impacting the skin, then stimulation of sub-dermal production of NO is implicitly obtained.
Shekhter et al. is discussed in detail above and that discussion is incorporated by reference.
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
1. The difference between the instant application and Nelson et al. is that Nelson et al. do not expressly teach stimulating sub-dermal production of NO or using from about 200 ppm to 1000 ppm gNO in methods of wound healing. This deficiency in Nelson et al. is cured by the teachings of Miller and Shekhter et al.
1. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform the method of Nelson et al. with from about 200 ppm to 1000 ppm gNO in methods of wound healing, as suggested by Miller, and stimulate sub-dermal production of NO, as taught by Shekhter et al., to produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because the references are directed to wound healing and Miller teaches that: “an effective amount of exogenous gaseous nitric oxide (gNO) in order to promote healing by reducing the size, duration and severity of wounds as well as controlling the infection by reducing number of pathogens at the site and the surrounding area” (Abstract) and suggests the narrow range of about 20-1000 ppm gaseous nitric oxide applied to the skin provides that therapeutic benefit. The same amount of applied nitric oxide to the dermal site of action produced by the same exogenous means a stream of gas generated by a plasma source will implicitly stimulate sub-dermal production of NO. This was verified by Schekhter et al. Accordingly, the ordinary artisan would optimize the parameters suggested by Nelson et al. and apply from about 200 ppm to 1000 ppm of nitric oxide at impact with the dermis of a stream of gas generated by a plasma source, along with the other chemical and physical components of the plasma stream to have a direct effect on any pathogens at the site of action and stimulate sub-dermal production of NO with a reasonable expectation of success.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the combined references, especially in the absence of evidence to the contrary.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Nelson et al. (US20160193336) as applied to claims 1-2, 4-10, 12 and 15-24 above.
Applicant claims:
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The reference of Nelson et al. is discussed in detail as applied to claims 1-2, 4-10, 12 and 15-24 above and that discussion is incorporated by reference. It is well settled that “a disclosure that anticipates under § 102 also renders the claim invalid under §103, for anticipation is the epitome of obviousness. See MPEP 1207.03(a)(II) states: “"lack of novelty is the epitome of obviousness." May, 574 F.2d at 1089, 197 USPQ at 607 (citing In re Pearson, 494 F.2d 1399, 1402, 181 USPQ 641, 644 (CCPA 1974))”. Accordingly, the claims rejected under §102 above are also invalid under §103.
The difference between the instant application and Nelson et al. is that Nelson et al. do not expressly teach directing the plasma-generated stream of gas for 5 to 60 seconds for each square centimeter of site area. However, Nelson et al. do teach a time period of 5 to 45 seconds for directing the stream of matter for each square centimeter of site area (Claim 3), which lies within the claimed range and renders it obvious. Nelson et al. further teach: “"Time of application" will be understood to be the amount of time, in seconds, that the NO-containing matter in a plasma state will be directed from the plasma device onto the treatment site, per square centimeter of site area. Thus, the time of application will depend upon the size of the area being treated.” [0077]. Thus, the time of application is a result effective variable optimized by the ordinary artisan and the ordinary artisan would perform the method of Nelson et al. for 5 to 60 seconds for each square centimeter of site area with a reasonable expectation of success.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Nelson et al. (US20170112871) is similar to Nelson et al. (US20160193336) above. The examiner has carefully compared the references with one another and with the applicant’s disclosure to avoid an unnecessary number of rejections over similar references. The examiner is not called upon to cite all references that may be available, but only the "best." (See 37 CFR 1.104(c).) Multiplying references, any one of which is as good as, but no better than, the others, adds to the burden and cost of prosecution and should therefore be avoided. See MPEP 904.03.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNST V ARNOLD whose telephone number is (571)272-8509. The examiner can normally be reached M-F 7-3:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian Y Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERNST V ARNOLD/Primary Examiner, Art Unit 1613
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