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 .
Response to Arguments
Applicant’s arguments, see “Applicant Arguments/Remarks” filed 01/06/2026, regarding the rejections under U.S.C. 103 are unpersuasive.
Applicant argues that the Examiner’s assertion in the previous office action regarding Figs. 5a and 5b cannot show that the tested subjects did not have diabetic retinopathy. The previous action noted that ICAM-1 levels and leukostasis levels of the diabetic subjects treated with PBM were at or lower than the non-diabetic control, which was used as evidence to support the previous claim that the subjects did not present with diabetic retinopathy, either NDPR or DPR. Applicant argues that nothing in Tang or in the state of the art supports this assertion. The Applicant’s arguments are unpersuasive. Tang is not directed to the treatment of diabetic retinopathy, Tang explicitly states that their research is “to determine if PBM might have value against diabetes induced damage to the retina” and they “investigated the effects of transient (4 minutes per day, 25mW/cm2, 7 J/cm2) phototherapy with far-red light on in vivo and in vitro pathological changes relevant to the development of diabetic retinopathy,” on Pg. 3681, last paragraph, emphasis added by the Examiner. For this statement to be accurate, the subjects could not have already developed diabetic retinopathy. The paragraph continues to explicitly state that leukostasis and ICAM-1 production are two of the types of diabetic-induced abnormalities causing damage done to the retina, the damage leading to diabetic retinopathy. Paragraph 0154 of Gast likewise indicates that this is knowledge well-known in the art. Therefore, if Tang’s control has equal levels of ICAM-1 and leukostasis production to the PBM treated diabetic, the damage needed to create diabetic retinopathy has not yet occurred, meaning the subject has never presented with diabetic retinopathy. This is further supported by the first paragraph of “Inflammation” section on Pg. 3686, as it further states these levels become elevated by diabetes, not by the development of diabetic retinopathy.
Further, the Examiner notes that the exact language of the claims is that the subject does not “present” with diabetic retinopathy, not that the subject does not have diabetic retinopathy. The Examiner provides arguments to Applicant’s current interpretation of their claim language for the purposes of furthering prosecution, and believes that Tang teaches either interpretation, as shown by the arguments above.
Next, Applicant argues that the differences in Gast’s phototherapy treatments (using photocoagulation) and Tang’s phototherapy treatment (photobiomodulation) renders the combination invalid, as one would not consider applying aspects of Gast’s photocoagulation method to Tang’s photobiomodulation method. This is unpersuasive. First, while Tang is teaching the benefits of photobiomodulation, they also explicitly state that photocoagulation is a known potential alternative to treat diabetic retinopathy (see first paragraph of the “Discussion” section on Pg. 3687), so it is unpersuasive to say that the treatment are so different that it would be non-obvious to use an aspect of one to benefit the other. However, the previous reliance on Gast has nothing to do with Gast’s photocoagulation. It is not being argued that because Gast teaches using photocoagulation to mitigate ICAM-1 in prediabetics that therefore one would use photobiomodulation to mitigate ICAM-1 in prediabetics. As shown by Tang, it is already taught that ICAM-1 production is mitigated in diabetic subjects to prevent or delay onset using photobiomodulation. The only thing Tang does not teach is treating as early as the pre-diabetes stage. As Gast teaches that mitigating ICAM-1 production is beneficial to prediabetics to prevent diabetic retinopathy, and Tang teaches that ICAM-1 production is mitigated in their phototherapy to prevent diabetic retinopathy, it is obvious that one of ordinary skill would apply Tang’s method to a prediabetic. As previously stated in the last action, the mechanism for causing diabetic retinopathy is exactly the same in a prediabetic or diabetic that develops diabetic retinopathy: hyperglycemia.
The Examiner also points out that while Tang does not teach treating specifically a prediabetic, Tang does teach using the photobiomodulation as a form of “preconditioning” to pre-treat and provide better outcomes for those at risk of future retinal harm, see the last paragraph on Pg. 3688 in the “Discussion” section. The Examiner notes this preconditioning explicitly refers an undamaged phase in the eye, i.e. before diabetes and the associated damage occurs. This shows that Tang knows the need for earlier prevention than the onset of diabetes, further making it obvious for one to use Tang’s method on a prediabetic.
For these reasons, the Examiner is maintaining the rejections to the Claims below. The rejections have been updated to address the amended limitations.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
i. Determining the scope and contents of the prior art.
ii. Ascertaining the differences between the prior art and the claims at issue.
iii. Resolving the level of ordinary skill in the pertinent art.
iv. 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 1, 3-11, 13-15, 18, 20-21, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over NPL awarded to Tang et al (cited on the IDS dated 06/30/2023), hereinafter Tang, in view of U.S. Patent Application 20190192345 awarded to Gast et al, hereinafter Gast.
Regarding Claim 1, Tang teaches a method for treatment of an eye of a subject (title), the method comprising: administering to the eye of the subject an effective amount of photobiomodulation (PBM) light effective for preventing or delaying onset of diabetic retinopathy (DR) (Pg. 3681, last paragraph, emphasis added by the Examiner, “to determine if PBM might have value against diabetes induced damage to the retina” and they “investigated the effects of transient (4 minutes per day, 25mW/cm2, 7 J/cm2) phototherapy with far-red light on in vivo and in vitro pathological changes relevant to the development of diabetic retinopathy,”), the PBM including light having a wavelength in a red wavelength range (abstract), wherein prior to administering the PBM light the subject is at-risk for developing DR (any form of hyperglycemia is a risk factor for DR); and the subject does not present with a mild to severe nonproliferative retinopathy and does not present with a proliferative diabetic retinopathy (In Vivo Studies, ‘Animals’ ¶2, “To ensure that the light therapy did not influence the severity of diabetes, PBM therapy was not initiated until diabetes was established (defined as three consecutive measures of non-fasting blood glucose > 275 mg/dL)”, treatment was started due to identification of diabetes, not NPDR, further supported by Figs. 5a/5b showing that the reference subjects and PBM treated diabetic subjects maintained near identical ICAM-1 and leukostasis levels, showing that blood flow was maintained and lack of additional adhesion occurred). Tang does not wherein the subject is prediabetic. Tang does teach that the photobiomodulation is likely successful in inhibiting diabetic retinopathy by inhibiting ICAM-1 production (see Results subheading in the Abstract).
However, in the art of preventing diabetic retinopathy, Gast teaches using a form of light therapy (photocoagulation) to prevent diabetic retinopathy in prediabetics (abstract, Para. 0013), to prevent retinal ischemia (Para. 0109), thereby reducing ICAM-1 production and preventing and/or delaying diabetic retinopathy (Para. 0154).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Tang by Gast, i.e. by treating with photobiomulation to inhibit diabetic retinopathy as in Tang on a pre-diabetic subject as in Gast, as one of ordinary skill would know based on the teachings of Gast that reducing/preventing ICAM-1 production in a prediabetic is beneficial, and Tang teaches the need for reducing/preventing ICAM-1 production, which Tang’s photobiomodulation is taught to accomplish.
Regarding Claim 3, Tang modified by Gast makes obvious the method of Claim 1. Tang further teaches wherein the red wavelength range is 670 +/- 50nm (abstract, 670 nm).
Regarding Claim 4, Tang modified by Gast makes obvious the method of Claim 1. Tang further teaches wherein the red wavelength range is 670 nm +/- 30nm (abstract, 670 nm).
Regarding Claim 5, Tang modified by Gast makes obvious the method of Claim 1. Tang further teaches wherein the PBM light consists essentially of light having a wavelength in a red wavelength range (abstract, 670 nm).
Regarding Claim 6, Tang modified by Gast makes obvious the method of Claim 1. Tang further teaches wherein the PBM light consists of light having a wavelength in a red wavelength range (abstract, 670 nm).
Regarding Claim 7, Tang modified by Gast makes obvious the method of Claim 1. Tang further teaches wherein the method further comprises administering to the eye of the subject an effective amount of PBM light comprising: … (ii) light having a wavelength in a near-infrared (NIR) wavelength range (670 nm is near-infrared, see Near-Infrared section).
Regarding Claim 8, Tang modified by Gast makes obvious the method of Claim 1. Tang further teaches wherein the subject is hyperglycemic (Under Death and Dysfunction of Retinal Neurons section, “Application of PBM to cells in hyperglycemic conditions produced a significant reduction in cell death to levels at or below controls in all cell types except ARPE19 cells”).
Regarding Claim 11, Tang modified by Gast makes obvious the method of Claim 1. Tang does not teach wherein the vascular endothelial growth factor is measured after the administration of the PBM light.
However, Gast teaches the negative impact VEGF has on diabetic retinopathy (Para. 0083).
It would have been obvious to one of ordinary skill in the art before the effective fling date of the claimed invention to modify Tang by Gast, i.e. by monitoring VEGF after PBM light treatment, for the predictable purpose of combining prior art elements of preventing DR according to known methods to yield predictable results for improving/maintaining eye health.
Regarding Claim 13, Tang modified by Gast makes obvious the method of Claim 1. Tang further teaches wherein the method comprises: (i) administering the PBM light to the eye at a dose of at least about 4.5 J/cm2 (see section under Fig. 6, 5 J/cm2, Pg. 4 Line 23 states “about” means +/- 20%, making the acceptable range 3.4-5.4 J/cm2);
Regarding Claim 14, Tang modified by Gast makes obvious the method of Claim 1. Tang further teaches wherein the method comprises administering the PBM light on one or more days in a one-week period (see Near-Infrared PBM section, “For comparison, some diabetic animals were treated only three times per week with 670 nm PBM”).
Regarding Claim 15, Tang modified by Gast makes obvious the method of Claim 14. Tang further teaches wherein the method further comprises administering the PBM light one or more times per week (See Near-Infrared PBM section, “For comparison, some diabetic animals were treated only three times per week with 670 nm PBM”) for two or more consecutive weeks (Method section states study lasted 10 weeks).
Regarding Claim 18, Tang modified by Gast makes obvious the method of Claim 1. Tang further teaches wherein the method further comprises, prior to and/or after administering the PBM light, performing one or more of: an electroretinogram (Introduction, “At the cellular level, PBM decreased retinal superoxide generation and inhibited diabetes-induced abnormalities of electroretinograms (ERGs)”).
Regarding Claim 20, Tang modified by Gast makes obvious the method of Claim 1, wherein the administering to the eye the effective amount of PBM light prevents or delays the onset of diabetic retinopathy by reducing or modulating, in the eye of the subject: (a) oxidative stress; (b) NFkB activity; and/or (c) ICAM-1 expression or activity (As it is set forth in the rejection to Claim 1 that Tang teaches the usage of PBM light to delay the onset of diabetic retinopathy, modulating or reducing (a)-(c) is an inherent method effect. Where a reference discloses the terms of the recited method steps, and such steps necessarily result in the desired and recited effect, that the reference does not describe the recited effect in haec verba is of no significance as the reference meets the claim under the doctrine of inherency. Ex Parte Novitski, 26 USPQ2d 1389, 1390-91 (BdPatApp & Inter 1993)).
Regarding Claim 21, Tang modified by Gast makes obvious the method of Claim 1, wherein the administering to the eye the effective amount of PBM light prevents or delays the onset of diabetic retinopathy by reducing or modulating, in the eye of the subject a mitochondrial membrane potential, a NADPH-dependent oxidoreductase activity level, or both (As it is set forth in the rejection to Claim 1 that Tang teaches the usage of PBM light to delay the onset of diabetic retinopathy, modulating or reducing the aforementioned components is an inherent method effect. Where a reference discloses the terms of the recited method steps, and such steps necessarily result in the desired and recited effect, that the reference does not describe the recited effect in haec verba is of no significance as the reference meets the claim under the doctrine of inherency. Ex Parte Novitski, 26 USPQ2d 1389, 1390-91 (BdPatApp & Inter 1993)).
Regarding Claim 23, Tang modified by Gast makes obvious the method of Claim 1, wherein prior to administering the PBM light, the eye of the subject has increase production, expression, and/or activity of (i) a reactive oxygen species (Tang Fig. 2 section, “We conducted in vitro studies to investigate effects of PBM on the death of several retinal cell types in high glucose. Cell lines were incubated in 5 mM glucose to simulate nondiabetic conditions or 30 mM glucose to simulate diabetic conditions, with or without 670 nm light treatment… Effects of PBM on superoxide generation and cell death in high glucose were found to be exposure dependent, PBM having no significant effect on either parameter at 50 seconds exposure, but significantly inhibiting both at 100- and 200-second exposures (inhibiting the glucose-induced increase in superoxide at the two exposure durations by 65% and 103%, respectively, and inhibiting the glucose-induced increase in cell death by 83% and 73%, respectively).”)
Claims 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over attached NPL awarded to Tang et al, hereinafter Tang, U.S. Patent Application 20190192345 awarded to Gast et al, hereinafter Gast, further in view of U.S. Patent 9062105 awarded to Clube, hereinafter Clube.
Regarding Claim 16, Tang modified by Gast makes obvious the method of Claim 1. Tang does not teach wherein the subject had previously received or is receiving an anti-VEGF therapy.
However, Clube teaches the usage of an anti-VEGF to prevent or inhibit DR progression (Col. 335, Lines 48-55, “Similarly, ocular diseases and conditions, such as AMD and DR are associated with angiogenesis, and inhibitors are useful for the treatment or prevention of these too. Thus, anti-VEGF (ie, VEGF-A) ligands and antibodies of the invention are useful for treating, preventing or reducing the risk of one or more of such ocular conditions and cancer (eg, solid tumours)”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Tang by Clube, i.e. by combining the anti-VEGF therapy of Clube with the PBM of Tang, for the predictable purpose of combining prior art elements of preventing DR according to known methods to yield predictable results for improving/maintaining eye health.
Regarding Claim 17, Tang modified by Gast and Clube makes obvious the method of Claim 16. Tang does not teach wherein if any one of (i)(a)-(i11) is indicative of or associated with the presence or progression of diabetic retinopathy and/or diabetic macular edema, the method comprises administering a further therapy comprising administration of the PBM light to the eye of the subject.
However, Tang does teach that PBM “essentially prevented” the expression of ICAM-1 levels increased by diabetes (Abstract) to reduce/prevent ICAM-1 mediated inflammation for the health of the retina (see Inflammation section).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Tang, i.e. by continuing treatment as long as ICAM-1 levels are detected, as Tang teaches the need to reduce/prevent ICAM-1 for eye health and teaches their method preforms this effect.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jess Mullins whose telephone number is (571)-272-8977. The examiner can normally be reached between the hours of 9:00 a.m. to 5:00 p.m. PST M-F.
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/JLM/
Examiner, Art Unit 3792
/UNSU JUNG/Supervisory Patent Examiner, Art Unit 3792