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 .
Election/Restrictions
Applicant’s election without traverse of Group I and Species A, claims 1-14 and 25 in the reply filed on January 09, 2026 is acknowledged. Claims 1-28 are pending. The non-elected claims 15-24 and 26-28 are withdrawn, and claims 1-14 and 25 are examined in this Office action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on February 26, 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement are considered by the examiner. Total 62 references filed in the IDS have been considered.
Applicant is reminded of the continuing obligation under 37 CFR 1.56, to timely apprise the Office of any information which is material to patentability of the claims under consideration in this application. IDS should be filed for all 72 references cited in the specification PG Pub US 2024/0268796 A1 [150] to [0221].
Drawings
The drawings filed on February 13, 2024 are accepted.
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 10, 12-14 and 25 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 pre-AIA the applicant regards as the invention.
Claim 10 recites “high vascularization” that renders the scope of the claim indefinite. The term “high” is a relative term which renders the claim indefinite. It is unclear how high of the vascularization is considered “high vascularization”. It is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 12 recites “which is operable to diagnose or monitor a disease or condition” that renders the scope of the claim indefinite. It is unclear what object the term “which” refers to. It should be specified whether it refers to the entire system or any components of the system.
Claim 14 recites “the system is further operable to diagnostically exclude that the disease or condition is cardiogenic shock” that renders the scope of the claim indefinite. The system may be operable to diagnose a disease or condition. However, the system would have no control in regard to what disease and condition that the subject carries. For example, if the subject has cardiogenic shock, it becomes unclear how the system may be operable to exclude that the disease or condition is cardiogenic shock. Clarification with proper amendment is required.
Claim 25: “the capillary bed” lacks proper antecedent basis.
The dependent claims of the above rejected claims are rejected due to their dependency.
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 1-4, 7, 9-11 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Suschek et al., “Non-enzymatic NO production in human skin: effect of UVA on cutaneous NO stores”. Nitric Oxide 22 (2010) 120-135, hereinafter Suschek.
Claim 1. Suschek teaches in FIGS.3-4 a system for determining levels of an S-nitrosothiol (p.131, Col. Left, ¶-2: two photolabile NO stores come to mind: S-nitrosothiols and nitrite anions. Both have broad UVA absorption bands) in situ by measuring nitric oxide released from a target site in the body of a mammal (p.130, Col. Right, Conclusions: the basal formation of NO was confirmed by two independent methods. In the first method, the NO radicals were trapped in situ in human skin biopts with iron-dithiocarbamate complexes and subsequently quantified with EPR spectroscopy. P.128, FIG.3: diagram for detection of gaseous NO emanating from the forearm skin of human volunteers) after exposure to ultraviolet light (p.131, Col. Left, ¶-2: the formation of NO could be enhanced 3- to 5-fold by illumination with UVA light, FIG.3), comprising:
a housing having a proximal end and a distal end and defining a cavity therebetween (p.127, Col.Right, No emanating from skin of human volunteers in dark: we developed a stainless-steel collection chamber for the accumulation of gases from a small area of human skin. The cylindrical airtight chamber covers a skin area),
the housing further defining an opening at the distal end, wherein the housing is configured for placement of the distal end in proximity with the target site to form a seal between the distal end of the housing and the target site, wherein a portion of the target site is exposed to the cavity through the opening (p.128, Col. Left, ¶-1: the chamber was placed on the thoroughly cleansed inner upper arm of volunteers; and FIG.3: the collection chamber is pressed to the skin by elastic bands);
a source of ultraviolet light affixed to the proximal end of the housing and positioned to irradiate the portion of the target site through the opening (p.128, Col. Left, ¶-1: the UVA transparent front window allows illumination of the underlying skin); and
a nitric oxide analyzer configured to receive a gas sample from the cavity following irradiation of the target site and operable to measure a nitric oxide concentration in the gas sample (FIG.3, legend: NO from the skin was accumulated in the chamber for 120s. The NO content of the chamber was quantified by flushing the contents with the trace gas into the CLD analyzer; and p.130, Col. Left, After UVA exposure: NO trapping experiments were also carried out with skin specimens that had been irradiated with UVA. In these irradiated samples we detected significantly higher MNIC yields, and p.128, Col. Right, NO emanating from human skin is enhanced by UVA: under illumination with a low-pressure UVA with narrow band emission at 365 nm, the collection chamber had accumulated a quantity of 260 ppb NO in argon).
As illustrated in FIG.3, the steel chamber is the housing. The space within is the cavity. The side that contacts the skin (the target site) is the distal end, and it is open to the target site (such that the air sample can be collected). The opposite side where the quartz glass is placed is the proximal end. The housing is pressed to the target site by the elastic bands (FIG.3 legend), which forms a seal between the distal end of the housing and the target site. Upon the housing being placed and pressed on the target site that faces the opening, a portion of the target site would be exposed to the cavity through the opening. The UV light is irradiated from the proximal end, through the quartz glass, the chamber, the opening, then to the target site. Hence the UV light source is considered being positioned to irradiate the portion of the target site through the opening.
In regard to the feature of the source of the UV light affixed to the proximal end of the housing, since the function of the UV light is to irradiate the target site though the opening, whether the source is affixed to the housing, or it is a distance from the housing, it would still provide the same function. As illustrated in FIG.3, the system is configured such that the UVA irradiates aiming the skin through the chamber. Such a limitation of the source being affixed to the proximal end of the housing is considered among various common practices that normally requires only ordinary skill in the art and hence are considered routine expedients depending on the overall design and configuration of the system. Such an alternate configuration is considered merely rearrangement of parts, which the court has held normally require only ordinary skill in the art and hence is considered routine expedients. In re Japikse, 181 F.2d 1019, 86 USPQ 70 (CCPA 1950) (Claims to a hydraulic power press which read on the prior art except with regard to the position of the starting switch were held unpatentable because shifting the position of the starting switch would not have modified the operation of the device.); In re Kuhle, 526 F.2d 553, 188 USPQ 7 (CCPA 1975) (the particular placement of a contact in a conductivity measuring device was held to be an obvious matter of design choice). MPEP 2144.04.VI.C.
Claim 2. Suschek further teaches that
the levels of the S-nitrosothiol in situ are determined based on a correlation with the nitric oxide concentration (p.131, Col. Left, ¶-2: two photolabile NO stores come to mind: S-nitrosothiols and nitrite anions…Both are known to deliver free NO radicals upon UVA photolysis) – since S-nitrosothiols delivers NO upon UVA photolysis, the concentration of NO is correlated to the level of S-nitrosothiols.
Claims 3-4 and 10. Suschek further teaches that
the target site is one or more of an organ, tissue, body cavity, and body fluid (claim 3); the target site is one or more of skin, oral cavity, and spinal fluid (claim 4) (FIG.3: the target site is the skin); and
the organ or tissue is an organ or tissue having high vascularization (claim 10) (the skin is a tissue of high vascularization. FIG.2 illustrates the dermal microvessels distribution in the skin dermis).
.
Claim 7. Suschek further teaches that
the ultraviolet light comprises light having a wavelength of from about 300 to about 375 nm (p.121, Col. Left, Table 1: band UVA has a wavelength range of 320-400 nm) – the range of 320-400 nm substantially overlaps with the claimed range.
Claim 9. Suschek further teaches that
the S-nitrosothiol is S-nitroso-l-cysteine or S-nitrosoglutathione (p.124, Col. Right, ¶-1: RSNOs like S-nitrosoalbumin, S-nitrosoglutathione or S-nitrosocysteine have been detected and quantified in vivo and are thought to be responsible for some of the well-documented physiological processes that previously had been attributed to NO itself).
Claim 11. In regard to the specific region of the skin as claimed, i.e., a finger or an ear, it is considered an intended use of the claimed system. Such a limitation does not further limit the structure of the claimed system. There is no recitation in the claim what structural limitation causes the system to be placed in any particular target site, including the recited finger or ear. As Suschek teaches that the skin is the skin of human thing, human soles of feet (Table 4, table legend), the forearm skin of human volunteers (FIG.3, figure legend), and skin from abdomen (p.129, Col. Right, ¶-1), it is considered reading on the limitation of the skin to be any portion of a human body as long as the dimension of the system can fit, which would include a finger and an ear. For the above consideration, see MPEP § 2114.II: "[A]pparatus claims cover what a device is, not what a device does." Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990). A claim containing a "recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus" if the prior art apparatus teaches all the structural limitations of the claim. Ex parte Masham, 2 USPQ2d 1647 (Bd. Pat. App. & Inter. 1987).
Claim 25. A method of measuring capillary bed perfusion in a subject in need thereof, comprising: using the system of claim 1 to measure S-nitrosothiol levels in the capillary bed of a tissue of the subject (p.120, Col. Left, Introduction, ¶-1: three different NOS isoforms have been characterized, eNOS, nNOS and iNOS; and last line: the eNOS isoform appears to be restricted to endothelial cells of the capillary bed of the dermis only) – as applied to claim 1, Suschek teaches a nitric oxide analyzer that detects NO from the skin. Since eNOS is one of the three isoforms of the NO being detected, the S-nitrosothiol level in the capillary bed is being measured.
Claims 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Suschek in view of Ehrick et al., US 2013/0161851 A1, hereinafter Ehrick.
Claims 5-6. Suschek teaches all the limitations of claims 1 and 15.
Suschek does not teach a lens affixed to the housing, the lens operable to focus the source of ultraviolet light upon the target site (claim 5), and the lens is a double convex focusing lens (claim 6).
However, in an analogous UV light irradiation field of endeavor, Ehrick teaches
a lens affixed to the housing, the lens operable to focus the source of ultraviolet light upon the target site, and the lens is a double convex focusing lens ([0059]: a lens 44, preferably having a double-convex configuration for facilitating extremely close focus, may be disposed between the at least one video device and the quartz window).
Therefore, it would have been obvious to one of the ordinary skilled in the art before the effective filing date of the claimed invention to have the system and method of Suschek employ such features of a lens affixed to the housing, the lens operable to focus the source of ultraviolet light upon the target site, and the lens is a double convex focusing lens as taught in Ehrick for the advantage of “reducing the possibility of glare due to light reflected from surfaces of the quartz viewing window, and to focus the UV light”, as suggested in Ehrick, [0059].
In regard to the lens being movably affixed to the housing, whether the lens are affixed in a movable or fixed way, it is considered among various common practices that normally requires only ordinary skill in the art and hence are considered routine expedients. Such an alternate configuration is considered merely rearrangement of parts, which the court has held normally require only ordinary skill in the art and hence is considered routine expedients. In re Larson, 340 F.2d 965, 968, 144 USPQ 347, 349 (CCPA 1965) (A claim to a fluid transporting vehicle was rejected as obvious over a prior art reference which differed from the prior art in claiming a brake drum integral with a clamping means, whereas the brake disc and clamp of the prior art comprise several parts rigidly secured together as a single unit. The court affirmed the rejection holding, among other reasons, "that the use of a one piece construction instead of the structure disclosed in [the prior art] would be merely a matter of obvious engineering choice."); but see Schenck v. Nortron Corp., 713 F.2d 782, 218 USPQ 698 (Fed. Cir. 1983) (Claims were directed to a vibratory testing machine (a hard-bearing wheel balancer) comprising a holding structure, a base structure, and a supporting means which form "a single integral and gaplessly continuous piece." Nortron argued that the invention is just making integral what had been made in four bolted pieces. The court found this argument unpersuasive and held that the claims were patentable because the prior art perceived a need for mechanisms to dampen resonance, whereas the inventor eliminated the need for dampening via the one-piece gapless support structure, showing insight that was contrary to the understandings and expectations of the art.). MPEP 2144.04.V.B. Making Integral, and In re Dulberg, 289 F.2d 522, 523, 129 USPQ 348, 349 (CCPA 1961) (The claimed structure, a lipstick holder with a removable cap, was fully met by the prior art except that in the prior art the cap is "press fitted" and therefore not manually removable. The court held that "if it were considered desirable for any reason to obtain access to the end of [the prior art’s] holder to which the cap is applied, it would be obvious to make the cap removable for that purpose."). MPEP 2144.04.V.C. Making Separable.
In regard to the focal length and the diameter of the lens, it is considered merely a design choice since the focal length is determined based on the distance of light source to the target site, and the diameter is determined based on the overall dimension requirement. The focal length and the diameter of the lens hence are considered among various common practices that normally requires only ordinary skill in the art and hence are considered routine expedients. Such an alternate configuration is considered merely rearrangement of parts, which the court has held normally require only ordinary skill in the art and hence is considered routine expedients. In re Rose, 220 F.2d 459, 105 USPQ 237 (CCPA 1955) (Claims directed to a lumber package "of appreciable size and weight requiring handling by a lift truck" were held unpatentable over prior art lumber packages which could be lifted by hand because limitations relating to the size of the package were not sufficient to patentably distinguish over the prior art.); In re Rinehart, 531 F.2d 1048, 189 USPQ 143 (CCPA 1976) ("mere scaling up of a prior art process capable of being scaled up, if such were the case, would not establish patentability in a claim to an old process so scaled." 531 F.2d at 1053, 189 USPQ at 148.). In Gardner v. TEC Syst., Inc., 725 F.2d 1338, 220 USPQ 777 (Fed. Cir. 1984), cert. denied, 469 U.S. 830, 225 USPQ 232 (1984), the Federal Circuit held that, where the only difference between the prior art and the claims was a recitation of relative dimensions of the claimed device and a device having the claimed relative dimensions would not perform differently than the prior art device, the claimed device was not patentably distinct from the prior art device. MPEP 2144.04.IV.A. Changes in size/proportion.
Claims 8 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Suschek in view of Gaston, IV et al., US 6,033,368, hereinafter Gaston, IV.
Claim 8. Suschek teaches all the limitations of claim 1.
Suschek does not teach that the nitric oxide analyzer performs a chemiluminescence-based assay.
However, in an analogous nitric oxide measurement field of endeavor, Gaston, IV teaches that
the nitric oxide analyzer performs a chemiluminescence-based assay (Col.6, ll.52-55: gas NO production rates were also measured by chemiluminescence over 5 minutes using a 765-liter sealed plethysmograph).
Therefore, it would have been obvious to one of the ordinary skilled in the art before the effective filing date of the claimed invention to have the nitric oxide analyzer of Suschek employ such features of “the nitric oxide analyzer performs a 64chemiluminescence-based assay” as taught in Gaston, IV for the advantage of a chemiluminescence assay well-recognized in the field of art, that is a high sensitivity, low background and low-cost assay platform.
Claim 12. Suschek teaches all the limitations of claim 1.
Suschek does not teach that the nitric oxide analyzer is operable to diagnose or monitor a disease or condition.
However, in an analogous nitric oxide measurement field of endeavor, Gaston, IV teaches that the nitric oxide analyzer is
operable to diagnose or monitor a disease or condition (Col.3, line 57 to Col.4, line 6: The device of the invention has several advantages, including…4. Clinical applicability in the setting of mechanically ventilated patient to easily monitor airway inflammation).
Therefore, it would have been obvious to one of the ordinary skilled in the art before the effective filing date of the claimed invention to have the nitric oxide analyzer of Suschek employ such features of “operable to diagnose or monitor a disease or condition” as taught in Gaston, IV for the advantage of carrying a clinical utility.
Claims 12 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Suschek in view of Seckler et al., US 2018/0164240 A1, hereinafter Seckler.
Claims 12-13. Suschek teaches all the limitations of claim 1.
Suschek does not teach that the nitric oxide analyzer is operable to diagnose or monitor a disease or condition.
However, in an analogous nitric oxide measurement field of endeavor, Seckler teaches that the nitric oxide analyzer is
operable to diagnose or monitor a disease or condition, and the disease or condition is sepsis ([0105]: suitable for detection or monitoring of nitrosothiol levels using the methods described herein, include…sepsis).
Therefore, it would have been obvious to one of the ordinary skilled in the art before the effective filing date of the claimed invention to have the nitric oxide analyzer of Suschek employ such features of “operable to diagnose or monitor a disease or condition, and the disease is sepsis” as taught in Seckler for the advantage of carrying a clinical utility for a specific medical condition.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Suschek in view of Seckler, further in view of de Werra eat al., “Cytokines, nitrite-nitrate, soluble tumor necrosis factor receptors, and procalcitonin concentrations – comparisons in patients with septic shock, cardiogenic shock, and bacterial pneumonia”. Critical Care Medicine 25(4):pp.607-613, April 1997, hereinafter de Werra.
Claim 14. Suschek and Seckler combined teaches all the limitations of claim 13.
Neither Suschek nor Seckler teaches that the system is further operable to diagnostically exclude that the disease or condition is cardiogenic shock.
However, in a nitric oxide based medical condition monitoring field of endeavor, de Werra teaches that the system is further operable to
diagnostically exclude that the disease or condition is cardiogenic shock (p.10, the last paragraph of the article: In conclusion…nitric oxide and high procalcitonin concentrations are found only in acute septic shock, and are not found in shock without infection or in severe infection alone) – Septic shock is one of the stage, or more specifically the most critical stage in sepsis. Cardiogenic shock is a shock without infection.
Therefore, it would have been obvious to one of the ordinary skilled in the art before the effective filing date of the claimed invention to have the nitric oxide analyzer of Suschek and Seckler combined employ such features of “operable to diagnostically exclude that the disease or condition is cardiogenic shock” as taught in de Werra for the advantage of carrying a clinical utility for identifying and differentiating among different medical conditions.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Barolet et al., “Light-induced nitric oxide release in the skin beyond UVA and blue light: read and near-infrared wavelengths”. Nitric Oxide 117 (2021) 16-25. This reference discloses a review that focuses on UVR, blue, red, and NIR spectra and their capacity to release NO in human skin.
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/YI-SHAN YANG/Primary Examiner, Art Unit 3798