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 .
Drawings
The drawings are objected to because the greyscale shading in Fig. 1 makes the words in the boxes/arrows difficult to read. Applicant should also consider removing the greyscale shading from Fig. 3 to ensure that the words in all of the boxes are clearly legible when reproduced.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 2 and 12 are objected to because of the following informalities:
Claim 2, the fourth line from the bottom should read “TcCO2”
Claim 12, items (xv) and (xvi) should read “TcCO2” (two instances in total)
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.
Claim 1, 2, 12, 42, 52, 91-96 and 99 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.
Regarding claim 1, 41 and 99 (and thus their dependent claims 2, 12, 42, 52 and 91-96), where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term “SpO2” is used by the claims to mean “a saturation of room air oxygen,” while the accepted meaning is “saturation of peripheral oxygen” in the blood. The term is indefinite because the specification does not clearly redefine the term, and it is unclear how a patient can “exhibit…room air oxygen.” For purposes of examination, the standard definition of SpO2 will be applied, i.e. it is a blood oxygen content measure, since the claims are understood to be preferring to patient parameters, not room conditions.
Regarding claims 2, 42 and 99 (and thus their dependent claims 12 and 52), it is unclear how the claims can (optionally, in the case of claim 2 and 42) include a step d/e of “continuing to wean the patient,” because claims 1, 41 and claim 99, line 13, already require “weaning the patient,” i.e. the independent claims require the patient to be weaned, such that it is unclear how weaning can continue if it has already occurred. As best understood, for purposes of examination, step b in claims 1, 41 and 99 will be considered to read “b. initializing weaning”.
Claim Interpretation
“Daytime hours” as recited in claims 1, 2, 41, 42 and 99 is understood in light of the instant specification at page 14, lines 22-25, and page 20, lines 24-25, to refer to the hours from 7am-7pm.
A “respiratory sprinting trial” as recited in claims 2, 12, 42, 52 and 99 is understood in light of the instant specification at page 18, lines 12-14, to mean a trial of spontaneous breathing.
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 (i.e., changing from AIA to pre-AIA ) 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:
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.
Claim(s) 1, 2, 41, 42 and 91-95 are rejected under 35 U.S.C. 103 as being unpatentable over Johnston and da Silva. Weaning and Extubation in Pediatrics. Current Respiratory Medical Reviews, 2012(8) 68-78 (hereinafter “Johnston”) in view of Childers et al. (US 2018/0369343 A1; hereinafter “Childers”).
Regarding claim 1, Johnston discloses a method of weaning a human patient that is on mechanical ventilation (abstract, section 2. Weaning), the method comprising:
a. determining that the patient exhibits (iii) a positive end-expiratory pressure of about 5 cmH20 or less on a ventilator ([t]o consider the beginning of the MV weaning process [i.e. the patient is on a ventilator]…gas exchanges [while on the ventilator] should be within acceptable parameters…positive end pressure [PEEP] ≤ 5 to 8 cmH2O, pg 69, col 1, 2. Weaning; see also Table 3); and
Johnston further suggests/teaches b. [initiating] weaning the patient off of mechanical ventilation during daytime hours (Girard et al. [54] recently published the results of a trial that employed a 'wake up and breathe' strategy in adults…a daily awakening trial followed by an [spontaneous breathing test], pg 72, col 2, para 1), because it would have been obvious to an artisan before the effective filing date of the claimed invention to initiate weaning (and associated spontaneous breathing trials) when a patient’s respiratory drive is most active (i.e. daytime), i.e. most likely to successfully respond to weaning, and/or medical personnel will have the time and/or alertness (i.e. at the beginning of a day shift) to track weaning progress.
While Johnston further teaches that patients should have the underlying disease corrected prior to weaning ([t]o consider the beginning of the MV weaning process, the disease that caused or contributed to the ventilation decompensation should be resolved or on the way to resolution, page 69, col. 1, 2. Weaning), Johnston is silent regarding where the patient has X-linked myotubular myopathy (XLMTM) off of mechanical ventilation, wherein the patient has previously been administered a therapeutically effective amount of a viral vector comprising a transgene encoding Myotubularin 1 (MTM1). However, Childers teaches that it was known in the respiratory therapy art before the effective filing date of the claimed invention to treat a patient on mechanical ventilation (patients are ventilator-dependent, para [0268]) that has X-linked myotubular myopathy (XLMTM) off of mechanical ventilation (a subject with X-linked myotubular myopathy (XLMTM), abstract), wherein the patient has been administered a therapeutically effective amount of a viral vector comprising a transgene encoding Myotubularin 1 (MTM1) (the present invention is useful for treating an individual with X-linked myotubular myopathy…improves muscle function and prolongs survival in afflicted subjects…the composition comprises a viral vector comprising a nucleic acid sequence encoding myotubularin…MTM1, paras [0048-49]), in order to improve breathing ability/correct the underlying cause of ventilation decompensation (paras [0013], [0043-46], [0054], [0270]). Therefore, it would have been obvious to one of ordinary skill in the art to modify the method of Johnston to include where the patient has X-linked myotubular myopathy (XLMTM) off of mechanical ventilation, wherein the patient has previously been administered a therapeutically effective amount of a viral vector comprising a transgene encoding Myotubularin 1 (MTM1) as taught by Childers, in order to provide the predictable result of initiating weaning in a ventilated patient of a known ventilator-dependent patient population who has received a therapy that may reduce or eliminate their ventilator dependency and who displays physiological parameters, e.g. gas exchanges, within known acceptable limits for initiating weaning (Johnston page 69, col. 1, 2. Weaning and Table 3).
Regarding claim 2, Johnston in view of Childers teaches the method of claim 1, wherein Johnston further discloses wherein:
(iii) the method comprises determining that the patient exhibits a positive end-expiratory pressure of about 5 cmH20 or less on a ventilator ([t]o consider the beginning of the MV weaning process [i.e. the patient is on a ventilator]…gas exchanges [while on the ventilator] should be within acceptable parameters…positive end pressure [PEEP] ≤ 5 to 8 cmH2O, pg 69, col 1, 2. Weaning; see also Table 3).
Regarding claim 41, Johnston discloses a method of treating a human patient that is on mechanical ventilation (abstract, section 2. Weaning), the method comprising:
(b) determining that the patient exhibits (iii) a positive end-expiratory pressure of about 5 cmH20 or less on a ventilator ([t]o consider the beginning of the MV weaning process…gas exchanges should be within acceptable parameters…positive end pressure [PEEP] ≤ 5 to 8 cmH2O, pg 69, col 1, 2. Weaning; see also Table 3); and
Johnston further suggests/teaches c. [initiating] weaning the patient off of mechanical ventilation during daytime hours (Girard et al. [54] recently published the results of a trial that employed a 'wake up and breathe' strategy in adults…a daily awakening trial followed by an [spontaneous breathing test], pg 72, col 2, para 1), because it would have been obvious to an artisan before the effective filing date of the claimed invention to initiate weaning (and associated spontaneous breathing trials) when a patient’s respiratory drive is most active (i.e. daytime), i.e. most likely to successfully respond to weaning, and/or medical personnel will have the time and/or alertness (i.e. at the beginning of a day shift) to track weaning progress.
While Johnston further teaches that patients should have the underlying disease corrected prior to weaning ([t]o consider the beginning of the MV weaning process, the disease that caused or contributed to the ventilation decompensation should be resolved or on the way to resolution, page 69, col. 1, 2. Weaning), Johnston is silent regarding treating a human patient that has XLMTM and the method comprising a. administering to the patient a therapeutically effective amount of a viral vector comprising a transgene encoding MTM1. However, Childers teaches that it was known in the respiratory therapy art before the effective filing date of the claimed invention to treat a patient on mechanical ventilation (patients are ventilator-dependent, para [0268]) that has XLMTM (a subject with X-linked myotubular myopathy (XLMTM), abstract) via a method comprising a. administering to the patient a therapeutically effective amount of a viral vector comprising a transgene encoding MTM1 (abstract; the present invention is useful for treating an individual with X-linked myotubular myopathy…improves muscle function and prolongs survival in afflicted subjects…the composition comprises a viral vector comprising a nucleic acid sequence encoding myotubularin…MTM1, paras [0048-49]), in order to improve breathing ability/correct the underlying cause of ventilation decompensation (paras [0013], [0043-46], [0054], [0270]). Therefore, it would have been obvious to one of ordinary skill in the art to modify the method of Johnston to include where the patient has XLMTM and the method comprising a. administering to the patient a therapeutically effective amount of a viral vector comprising a transgene encoding MTM1 myotubularin 1 (MTM1) as taught by Childers, in order to provide the predictable result of treating a ventilated patient of a known ventilator-dependent patient population with a therapy that may reduce or eliminate their ventilator dependency, then initiating weaning when the patient displays physiological parameters, e.g. gas exchanges, within known acceptable limits for initiating weaning (Johnston page 69, col. 1, 2. Weaning and Table 3).
Regarding claim 42, Johnston in view of Childers teaches the method of claim 41, wherein Johnston further discloses wherein:
(iii) the method comprises determining that the patient exhibits a positive end-expiratory pressure of about 5 cmH20 or less on a ventilator ([t]o consider the beginning of the MV weaning process [i.e. the patient is on a ventilator]…gas exchanges [while on the ventilator] should be within acceptable parameters…positive end pressure [PEEP] ≤ 5 to 8 cmH2O, pg 69, col 1, 2. Weaning; see also Table 3).
Regarding claim 91, Johnston in view of Childers teaches the method of claim 1, wherein Childers further educates modified Johnston to include wherein the viral vector is selected from the group consisting of adeno-associated virus (AAV), adenovirus, lentivirus, retrovirus, poxvirus, baculovirus, herpes simplex virus, vaccinia virus, and a synthetic virus (Childers para [0011]), in order to utilize a known type of viral vector to provide the predictable result of systemic delivery of the transgene (Childers paras [0009-11]).
Regarding claim 92, Johnston in view of Childers teaches the method of claim 91, wherein Childers further educates modified Johnston to include wherein the viral vector is an AAV (Childers para [0011]), in order to utilize a known type of viral vector to provide the predictable result of systemic delivery of the transgene (Childers paras [0009-11]).
Regarding claim 93, Johnston in view of Childers teaches the method of claim 92, wherein Childers further educates modified Johnston to include wherein the AAV is an AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAVrh10, or AAVrh74 serotype (Childers para [0011]), in order to utilize a known type of viral vector to provide the predictable result of systemic delivery of the transgene (Childers paras [0009-11]).
Regarding claim 94, Johnston in view of Childers teaches the method of claim 91, wherein the viral vector is a pseudotyped AAV (Childers para [0185]), in order to utilize a known type of viral vector to provide the predictable result of systemic delivery of the transgene (Childers paras [0009-11]).
Regarding claim 95, Johnston in view of Childers teaches the method of claim 94, wherein Childers further educates modified Johnston to include wherein the pseudotyped AAV is AAV2/8 or AAV2/9, optionally wherein the pseudotyped AAV is AAV2/8 (Childers para [0185]), in order to utilize a known type of viral vector to provide the predictable result of systemic delivery of the transgene (Childers paras [0009-11]).
Claim(s) 12 and 52 are rejected under 35 U.S.C. 103 as being unpatentable over Johnston in view of Childers as applied to claims 2 and 42 above, and further in view of Solsona et al. A pilot study of a new test to predict extubation failure. Crit. Care. 2009, 13(2):R56, pp 1-9 (hereinafter “Solsona”) and Eweje et al. (US 2022/0288333 A1; hereinafter “Eweje”).
Regarding claims 12 and 52, Johnston in view of Childers teaches the methods of claim 2 and 42, wherein Johnston further teaches performing respiratory sprinting trials/spontaneous breathing trials (SBTs) (page 69, 3. Spontaneous Breathing Trial) in conjunction with weaning (page 69, 2. Weaning), and that respiratory distress (Table 1), petCO2 (page 71, col 1), and SpO2 (Fig. 1) were known to be used in SBTs/assessing weaning qualification/progression, but modified Johnston is silent regarding wherein:
in the alternative, (i)-(xi) as claimed [limitations not recited individually here to save space].
However, optimization of ranges of parameters within prior art ranges or through routine experimentation is not sufficient to patentably distinguish the invention over the prior art see MPEP § 2144.05, and Solsona teaches that it was known in the ventilator weaning art before the effective filing date of the claimed invention to utilize in an SBT/weaning method wherein:
(ix) the method comprises determining that the patient exhibits no intercostal retraction (intercostal retractions…were monitored, page 2, right col; Table 1; variable independently associated with extubation failure was intercostal retraction, page 3, right col, fifth para; which infers that no intercostal retraction is an indicator that weaning is progressing/successful) in a respiratory sprinting trial (page 2, col 1);
(xi) the method comprises determining that the patient exhibits no respiratory paradox (no signs of…paradoxical breathing, page 2, col 1, fourth full para) in respiratory sprinting trial (page 2, col 1);
(xiii) the method comprises determining that the patient exhibits an SpO2 within an acceptable range (pulse oximetry more than 90%, page 2, col 1, fourth full para; see mean values in Table 1) as assessed by a respiratory sprinting trial (page 2, col 1);
(xiv) the method comprises determining that the patient exhibits an SpO2 that does not differ by greater than 3% relative to the patient's awake baseline (Table 1) as assessed by a respiratory sprinting trial (page 2, col 1);
(xv) the method comprises determining that the patient exhibits a pCO2 of greater than 45 mmHg (Table 1) as assessed by a respiratory sprinting trial (page 2, col 1);
(xvi) the method comprises determining that the patient exhibits a pCO2 that does not increase by 10 mmHg or more (Table 1) relative to the patient's awake baseline as assessed by a respiratory sprinting trial (page 2, col 1);
(xviii) the method further comprises determining that the patient exhibits no distress (no signs of…agitation, page 2, col 1, fourth full para) in a respiratory sprinting trial (page 2, col 1); and Eweje teaches that it was known in the ventilator weaning art before the effective filing date of the claimed invention that signs of increased work of breathing include tachypnea (para [0039]), and to include a video recording of a respiratory sprinting trial (paras [0037], [0041], [0053], [0120]). Therefore, it would have been obvious to an artisan before the effective filing date of the claimed invention for modified Johnston to include (ix) the method comprises determining that the patient exhibits no intercostal retraction in a video recording of a respiratory sprinting trial; (x) the method comprises determining that the patient exhibits no tachypnea in a video recording of a respiratory sprinting trial; (xi) the method comprises determining that the patient exhibits no respiratory paradox in a video recording of a respiratory sprinting trial; (xiii) the method comprises determining that the patient exhibits an SpO2 of less than 94% as assessed by a video recording of a respiratory sprinting trial; (xiv) the method comprises determining that the patient exhibits an SpO2 that does not differ by greater than 3% relative to the patient's awake baseline as assessed by a video recording of a respiratory sprinting trial; (xv) the method comprises determining that the patient exhibits a TcCO2 of greater than 45 mmHg as assessed by a video recording of a respiratory sprinting trial; (xvi) the method comprises determining that the patient exhibits a TcCO2 that does not increase by 10 mmHg or more relative to the patient's awake baseline as assessed by a video recording of a respiratory sprinting trial; or (xviii) the method further comprises determining that the patient exhibits no distress in a video recording of a respiratory sprinting trial as taught by Johnston, Solsona and Eweje, in order to monitor and record parameters that were well-known in the ventilator weaning art before the effective filing date of the claimed invention to be indicators of how weaning is likely to progress/progressing and compare them with known or determined-through-routine-experimentation values/thresholds to provide the predictable results of informing the care giver of the patient’s status and/or weaning likelihood of success/progression, as well as to provide a record and/or means of assessing the patient’s status remotely and/or for later analysis.
Claim(s) 96 is rejected under 35 U.S.C. 103 as being unpatentable over Johnston in view of Childers as applied to claim 1 above, and further in view of Bolen et al. (US 2023/0157955 A1; hereinafter “Bolen”).
Regarding claim 96, Johnston in view of Childers teaches the method of claim 1, but modified Johnston is silent regarding wherein the viral vector is resamirigene bilparvovec. However, it has been held to be within the general skill of one in the art to select a known material on the basis of its suitability for the intended use, see MPEP 2144.07, and Bolen teaches that it was known in the art of treating XLMTM/viral vectors before the effective filing date of the claimed invention for a viral vector comprising a transgene encoding Myotubularin 1 (MTM1) for XLMTM treatment to be resamirigene bilparvovec (middle of Table 2). Therefore, it would have been obvious to an artisan before the effective filing date of the claimed invention for modified Johnston to include wherein the viral vector is resamirigene bilparvovec as taught by Bolen, in order to provide the predictable result of a suitable viral vector comprising a transgene encoding MTM1 for XLMTM treatment (Bolen Table 2).
Claim(s) 99 is rejected under 35 U.S.C. 103 as being unpatentable over Johnston in view of Childers, Robert and Argaud. Chapter 10: Noninvasive Positive Ventilation. Obstructive Sleep Apnea: Diagnosis and Treatment. Informa Healthcare USA, Inc., (2007), 173-189 (hereinafter “Robert”), Annoussamy et al. X-linked myotubular myopathy: A prospective international natural history study. Neurology. 2019, 92(16) e1852-e1867 (hereinafter “Annoussamy”), Lain et al. (WO 2010/150264 A1; hereinafter “Lain”), Solsona and Eweje.
Johnston discloses a method of weaning a human patient that is on mechanical ventilation (abstract, section 2. Weaning), the method comprising:
a. determining that the patient exhibits (iii) a positive end-expiratory pressure of about 5 cmH20 or less on a ventilator ([t]o consider the beginning of the MV weaning process [i.e. the patient is on a ventilator]…gas exchanges [while on the ventilator] should be within acceptable parameters…positive end pressure [PEEP] ≤ 5 to 8 cmH2O, pg 69, col 1, 2. Weaning; see also Table 3); and
Johnston further suggests/teaches b. [initiating] weaning the patient off of mechanical ventilation during daytime hours (Girard et al. [54] recently published the results of a trial that employed a 'wake up and breathe' strategy in adults…a daily awakening trial followed by an [spontaneous breathing test], pg 72, col 2, para 1), because it would have been obvious to an artisan before the effective filing date of the claimed invention to initiate weaning (and associated spontaneous breathing trials) when a patient’s respiratory drive is most active (i.e. daytime), i.e. most likely to successfully respond to weaning, and/or medical personnel will have the time and/or alertness (i.e. at the beginning of a day shift) to track weaning progress.
While Johnston further teaches that patients should have the underlying disease corrected prior to weaning ([t]o consider the beginning of the MV weaning process, the disease that caused or contributed to the ventilation decompensation should be resolved or on the way to resolution, page 69, col. 1, 2. Weaning), Johnston is silent regarding where the patient has XLMTM off of mechanical ventilation, wherein the patient has previously been administered a therapeutically effective amount of an AAV2/8 viral vector comprising a transgene encoding MTM1 operably linked to a desmin promotor. However, Childers teaches that it was known in the respiratory therapy art before the effective filing date of the claimed invention to treat a patient on mechanical ventilation (patients are ventilator-dependent, para [0268]) that has X-XLMTM off of mechanical ventilation (a subject with X-linked myotubular myopathy (XLMTM), abstract), wherein the patient has been administered a therapeutically effective amount of a viral vector comprising an AAV2/8 viral vector comprising a transgene encoding MTM1 operably linked to a desmin promotor (the present invention is useful for treating an individual with X-linked myotubular myopathy…improves muscle function and prolongs survival in afflicted subjects…the composition comprises a viral vector comprising a nucleic acid sequence encoding myotubularin…MTM1, paras [0048-49]; the use of AAVs is a common mode of exogenous delivery of DNA…exemplary AAVs…suitable for the expression of myotubularin, include AAV2/8, paras [0099-100]); AAV…operably linked to a muscle specific promotor, claim 31; [t]issue-specific promotors, which can be included in the vector of the invention to drive expression specifically in muscle are known in the art, and include, but are not limited to a desmin promotor, para [0110]; see also paras [0222] and [0260]), in order to improve breathing ability/correct the underlying cause of ventilation decompensation (paras [0013], [0043-46], [0054], [0270]). Therefore, it would have been obvious to one of ordinary skill in the art to modify the method of Johnston to include where the patient has XLMTM off of mechanical ventilation, wherein the patient has previously been administered a therapeutically effective amount of an AAV2/8 viral vector comprising a transgene encoding MTM1 operably linked to a desmin promotor as taught by Childers, in order to provide the predictable result of initiating weaning in a ventilated patient of a known ventilator-dependent patient population who has received a therapy that may reduce or eliminate their ventilator dependency and who displays physiological parameters, e.g. gas exchanges, within known acceptable limits for initiating weaning (Johnston page 69, col. 1, 2. Weaning and Table 3).
While Johnston further teaches performing respiratory sprinting trials/spontaneous breathing trials (SBTs) (page 69, 3. Spontaneous Breathing Trial) in conjunction with weaning (page 69, 2. Weaning), and that maximal inspiratory and expiratory pressures (MIP/MEP) (including a MIP of 50 cmH2O) (page 73, col 1 and page 74, col 1, line 2), petCO2 (page 71, col 1), SpO2 (Fig. 1), blood pH (Fig. 1), and respiratory distress (Table 1) were known to be used in SBTs/assessing weaning qualification/progression [relevant to claimed a. i-vii and c. i-iii and viii-xi], modified Johnston is silent regarding
a. determining that the patient exhibits (i) a maximal inspiratory pressure (MIP) of about 50 cmH2O or more on a ventilator, (ii) a maximal expiratory pressure (MEP) of about 40 cmH20 or more on a ventilator, (iv) an SpO2 of about 94% or more, (v) a TcCO2 of from about 35 mmHg to about 45 mmHg, (vi) a petCO2 of from about 35 mmHg to about 45 mmHg, (vii) a serum bicarbonate level of from about 22 mEq/L to about 27 mEq/L, (viii) vital signs and a weight that are within age-adjusted norms, and (ix) a motor function score on the CHOP INTEND of greater than 45 or that neuromuscular development milestones have been met;
c. determining that the patient exhibits (i) a TcCO2 of from about 35 mmHg to about 45 mmHg as assessed by nocturnal respiration monitoring, (ii) a petCO2 of from about 35 mmHg to about 45 mmHg as assessed by nocturnal respiration monitoring, (iii) an SpO2 of about 94% or more as assessed by nocturnal respiration monitoring, (iv) no intercostal retraction in a video recording of a respiratory sprinting trial, (v) no tachypnea in a video recording of a respiratory sprinting trial, (vi) no respiratory paradox in a video recording of a respiratory sprinting trial, (vii) no phase delay in a video recording of a respiratory sprinting trial, (viii) an SpO2 of less than 94% as assessed by a video recording of a respiratory sprinting trial, (ix) an SpO2 that does not differ by greater than 3% relative to the patient's awake baseline as assessed by a video recording of a respiratory sprinting trial, (x) aTCO2 of greater than 45 mmHg as assessed by a video recording of a respiratory sprinting trial, (xi) a TCO2 that does not increase by 10 mmHg or more relative to the patient's awake baseline as assessed by a video recording of a respiratory sprinting trial, (xii) a respiration rate that is within age-adjusted norms as assessed by nocturnal respiration monitoring, (xiii) no distress in a video recording of a respiratory sprinting trial, and (xiv) a respiration rate that is within age-adjusted norm as assessed by PSG performed with an open tracheostomy; and
d. continuing to wean the patient off of mechanical ventilation during daytime hours.
However, optimization of ranges of parameters within prior art ranges or through routine experimentation is not sufficient to patentably distinguish the invention over the prior art, see MPEP § 2144.05, Robert teaches that it was known in the respiratory monitoring and assessment art before the effective filing date of the claimed invention that ventilator patients may be tracheotomized (page 173, first para), that known indicators of ventilation status include not only SpO2, etCO2, and blood pH as disclosed by Johnston, but also TcO2 and serum bicarbonate levels (page 175, second para; top of page 178), and to perform nocturnal respiratory monitoring of said parameters using a PSG (page 179, lines 7-15) [relevant to claimed a. iv-vii and c. i-iii, vii-xi and xiv], Annoussamy teaches that it was known in the XLMTM therapy art before the effective filing date of the claimed invention to evaluate patients using MEP, MIP, vital signs and weight compared to age-adjusted norms (pg e1853, col 2, para 2-6 "At each visit, the physician performed a complete physical examination, noted concomitant treatments and adverse events, measured vital signs, weight and height, and assessed ophthalmoplegia and ptosis…Patients older than 6 years without tracheostomy underwent pulmonary function tests measuring forced vital capacity (FVC)"; pg e1854, col 2, para 6 pg e1855, coll 1, para 1 - "All patients, including patients with a mild phenotype had abnormal pulmonary function with FVC, FEV1, MEP, MIP, and PCF lower than 80% of normal."; Table 2 - "Height, percentile Weight, percentile"), as well as motor function score on the CHOP INTEND (pg e1854, col 1, para 2 "To assess motor function, children younger than 2 years of age performed the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) scale"; Table 2 "CHOP- INTEND Mild 41 Intermediate 37 Severe 27.5") [relevant to claimed a. i, ii, viii and ix and c. xii and xiv), Lain teaches that it was known in the weaning art before the effective filing date of the claimed invention for weaning to take into account respiratory rate, heart rate, etCO2 (with 28-44 mmHg as a target for initiating weaning) and SpO2 (with greater than 94% or 90-94% as targets for initiating weaning) (page 21, lines 16-32; page 35, lines 28-30), with targets corrected for age (page 30, lines 22-26; page 40, line 24-page 41, line 29) and that are measured continuously and particularly within 12 hours of SBT/weaning, which would thus include the nocturnal hours before a morning weaning assessment (page 34, lines 25-28; page 27, lines 28-32) [relevant to claimed a. iv-vi and viii and c. i-iii, viii-xii and xiv], and Johnston, Solsana and Eweje are relevant to claimed c. iv-xi and xiii as discussed above regarding claims 12 and 52, where their discussion of assessing breathing abnormalities would have also reasonably suggested looking for no phase delay as an indication of a normal breathing pattern. Therefore, it would have been obvious to an artisan before the effective filing date of the claimed invention for modified Johnston to include a. determining that the patient exhibits (i) a maximal inspiratory pressure of about 50 cmH2O or more on a ventilator, (ii) a maximal expiratory pressure of about 40 cmH20 or more on a ventilator, (iv) an SpO2 of about 94% or more, (v) a TcCO2 of from about 35 mmHg to about 45 mmHg, (vi) a petCO2 of from about 35 mmHg to about 45 mmHg, (vii) a serum bicarbonate level of from about 22 mEq/L to about 27 mEq/L, (viii) vital signs and a weight that are within age-adjusted norms, and (ix) a motor function score on the CHOP INTEND of greater than 45 or that neuromuscular development milestones have been met; c. determining that the patient exhibits (i) a TcCO2 of from about 35 mmHg to about 45 mmHg as assessed by nocturnal respiration monitoring, (ii) a petCO2 of from about 35 mmHg to about 45 mmHg as assessed by nocturnal respiration monitoring, (iii) an SpO2 of about 94% or more as assessed by nocturnal respiration monitoring, (iv) no intercostal retraction in a video recording of a respiratory sprinting trial, (v) no tachypnea in a video recording of a respiratory sprinting trial, (vi) no respiratory paradox in a video recording of a respiratory sprinting trial, (vii) no phase delay in a video recording of a respiratory sprinting trial, (viii) an SpO2 of less than 94% as assessed by a video recording of a respiratory sprinting trial, (ix) an SpO2 that does not differ by greater than 3% relative to the patient's awake baseline as assessed by a video recording of a respiratory sprinting trial, (x) aTCO2 of greater than 45 mmHg as assessed by a video recording of a respiratory sprinting trial, (xi) a TCO2 that does not increase by 10 mmHg or more relative to the patient's awake baseline as assessed by a video recording of a respiratory sprinting trial, (xii) a respiration rate that is within age-adjusted norms as assessed by nocturnal respiration monitoring, (xiii) no distress in a video recording of a respiratory sprinting trial, and (xiv) a respiration rate that is within age-adjusted norm as assessed by PSG performed with an open tracheostomy; and d. continuing to wean the patient off of mechanical ventilation during daytime hours, through routine experimentation and in view of known weaning/SBT parameters as taught by Johnston, Robert, Annoussamy, Lain, Solsana and Eweje using standard equipment (i.e. including a PSG), to provide the predictable results of a comprehensive initial weaning assessment using data from an immediately prior time period, i.e. nocturnal monitoring for the morning weaning taught by Childers, to ensure relevant data and weaning progression/SBT analysis using known and video-recorded parameters, on a ventilated tracheostomy patient as a known patient population, to provide the predictable results of informing the care giver of the patient’s status and/or weaning likelihood of success and progression, as well as to provide a record and/or means of assessing the patient’s status remotely and/or for later analysis, and to continuing weaning (i.e. within the same day/daytime hours) as long as relevant parameters are within acceptable corrected norms/known or determined-through-routine-experimentation values/thresholds that indicate that the patient is able to successfully support their own ventilation.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Additional reference teaching morning/daytime weaning: Rosenfeld et al. (WO 00/79466 A2; page 75, lines 12-14). Additional references teaching known weaning/SBT criteria: Clemmer et al. (US 6,148,814); Doyle et al. (US 2011/0213215 A1); Errico et al. (WO 2021/110576 A1); Freeman et al. (US 2018/0280646 A1); Gadgil et al. (US 2020/0179206 A1); Habashi (US 2015/0068526 A1 and US 2006/0174884 A1); Jafari et al. (US 2014/0235959 A1); Kuronen et al. (US 2020/0155898 A1); Lachmann et al. (US 5,752,509); Morejon (US 2016/0199608 A1); Milne (US 2014/0150796 A1 and US 2014/0060540 A1); Sheinhauer et al. (US 2014/0000609 A1); Tehrani (US 2008/0236582 A1); Vandine et al. (US 2011/0041850 A1); MacIntyre et al. Evidence-Based Guidelines for Weaning and Discontinuing Ventilatory Support. Chest 2001, 120(6) Supp 375S-395S.
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/KATHRYN E DITMER/ Primary Examiner, Art Unit 3785