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 . 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.
Information Disclosure Statement
The information disclosure statement filed 26 Feb, 2026 fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because one reference was not found in the application file, and another reference was illegible. The PubChem reference was not legible, so it was not considered. Please note that, after uploading documents to the USPTO server, they are transferred to a different file type, with some loss of resolution. While the document uploaded to the server may have been legible, the document in the application file is not.
Election/Restrictions
Applicant elected intratracheal administration of an exogenous surfactant, vascular administration of rhodamine to patients under mechanical ventilation without traverse in the phone call with Eric Bleich, applicant’s representative, on 11 Feb, 2026.
Claims Status
Claims 44-63 are pending.
Claims 50 and 51 have been amended.
Claims 62 and 63 are new.
Claims 48, 51-60, 62, and 63 have been withdrawn due to an election/restriction requirement.
Claim Rejections - 35 USC § 112(b)
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 44-47, 49, 50, and 61 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.
Claim 44, and claims dependent on it, require a surface tension lowering component, while claim 50 states that it can be a rhodamine dye. A surfactant (i.e. a surface lowering agent) is a chemical with a hydrophobic section and a hydrophilic section (Liu et al, Curr. Opin. Colloid Interface. Sci. (2020) 45 p14-27, p14, 1st column, 1st paragraph). Rhodamine dyes are a family of triphenylmethane dyes where each ring has a charged or hydrophilic moiety on it (note the example of paragraph 44). Applicant’s prior work shows that rhodamine, by itself, does not lower surface tension (Perlman, US 20160067210, cited by applicant, paragraph 68), and converting a rhodamine to a surfactant in the prior art requires adding a hydrophobic moiety (McWilliams et al, Pure Appl. Chem. (2020) 92(2) p265-274, reaction scheme, table 1, p269, center of page). As applicant has stated in their claims that rhodamine is a surface tension lowering component, a property it does not have, it is unclear what applicant means by the phrase “surface tension lowering component.”
response to applicant’s arguments
Applicant argues that the claims have been amended to require a solution of rhodamine dye, rather than the dye itself.
Applicant's arguments filed 21 May, 2026 have been fully considered but they are not persuasive.
It is not clear how this overcomes the rejection. It is clear from the claim language that rhodamine is considered a surface tension lowering compound for purposes of the application, but this is a class of compounds that simply does not have that property. This makes it unclear if, for example, fluorescein, a chemically very similar compound to rhodamine that is commonly used in biological studies, is considered a surface tension lowering agent.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 44-47, 49, 50, and 61 are rejected under 35 U.S.C. 103 as being unpatentable over (Perlman, US 20160067210, cited by applicant) in view of Le Tourneau et al (J. Natl. Cancer Inst. (2009) 101 p708-720).
Perlman discusses rhodamine dyes to reduce aveolar surface tension (title), to reduce aveolar edema liquid (paragraph 19) during mechanical ventilation (paragraph 20), applicant’s elected patient population. This requires albumin (paragraph 68), either from the patient or administered with the rhodamine. This can be administered by the vasculature (paragraph 106), corresponding to part (ii) of claim 44. A mention is made of the benefits of tracheal instillation of an exogenous surfactant, such as Survanta, providing effects similar to that of the rhodamine (paragraph 84), step (i) of claim 44.
The difference between this reference and the examined claims is that this reference does not discuss both step (i) and step (ii) of examined claim 44 used together, nor does it discuss their timewise relationship.
Le Tourneau et al state that the main goal of the phase 1 clinical trial is to establish the dose and/or dose schedule for new drugs or drug combinations (abstract), to avoid unnecessary exposure of patients to subtherapeutic doses while preserving safety and maintaining rapid accrual (p708, 1st column, 2nd paragraph). A number of different experimental designs for establishing these numbers are mentioned (fig 2, p711, top of page). This reference discusses optimizing the dose schedule.
It is considered obvious to combine two moieties used for the same purpose (MPEP 2144.06(I)); in this case, the tracheal administration of exogenous surfactant formulation with vascular administration of rhodamine. This is a combination of known elements (the administration of each formulation separately) yielding expected results (lower surface tension in the avelolar space).
Furthermore, it would be obvious to optimize the dose and dose schedule of the combination, to avoid unnecessary exposure of patients to subtherapeutic doses while preserving safety and maintaining rapid accrual, as discussed by Le Tourneau et al. As every drug and drug combination must have these parameters optimized, a person of skill in the art would reasonably be experienced in this optimization, leading to a reasonable expectation of success.
Perlman renders obvious tracheal administration of an exogenous surfactant and vascular administration of rhodamine, rendering obvious claims 44, 49, and 50.
Le Tourneau et al renders obvious optimizing the dose schedule, rendering obvious claims 45-47 and 50.
Perlman renders obvious mechanical ventilation, rendering obvious claim 61.
response to applicant’s arguments
Applicant argues that the compounds used in the method are not toxic, so Le Tourneau et al is non-analogous art.
Applicant's arguments filed 21 May, 2026 have been fully considered but they are not persuasive.
There are two issues here. First, applicant has provided no evidence that the materials used in the claim are non toxic. Given that everything is toxic, if the dose is large enough; the dose makes the poison (Humble, AZ dept of Health Services blog, post of 19 June, 2019, 1st paragraph), this is not credible. Note that Kelner (West. J. Med. (1985) 143 p523-524) states that rhodamine is too toxic and carcinogenic to be used in food (p523, 1st column, 1st paragraph); this strongly suggests that toxicity is an issue. Second, toxicity is not the only endpoint. Le Tourneau et al discuss using efficacy for an endpoint for compounds that have limited toxicity (p708, 2nd column, 1st paragraph). In any event, a person of skill in the art will need to optimize the dose and dose schedule; Le Tourneau et al teaches how to do that, making it clearly relevant to the invention. It also should be noted that Le Tourneau et al is relied upon only for dose and dose schedule limitations; many of the claims lack such limitations.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
first rejection
Claims 44-47, 49, 50, and 61 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 12, and 13 of U.S. Patent No. 10,391,151 in view of Le Tourneau et al (J. Natl. Cancer Inst. (2009) 101 p708-720).
Competing claim 1 describes a method of reducing ventilation injury (i.e. on a ventilator or will be placed on a ventilator) of a patient with aveolar flooding, comprising administering a surfactant protein C. Competing claim 2 specifies that the material can be natural, recombinant, or synthetic, and competing claim 3 gives non-natural variants of the protein (i.e. exogenous). Competing claim 12 specifies tracheal administration, while competing claim 13 specifies vascular administration.
The difference between the competing claims and the examined claims is that this reference does not discuss both vascular and airway administration together, nor does it discuss their timewise relationship.
Le Tourneau et al state that the main goal of the phase 1 clinical trial is to establish the dose and/or dose schedule for new drugs or drug combinations (abstract), to avoid unnecessary exposure of patients to subtherapeutic doses while preserving safety and maintaining rapid accrual (p708, 1st column, 2nd paragraph). A number of different experimental designs for establishing these numbers are mentioned (fig 2, p711, top of page). This reference discusses optimizing the dose schedule.
It is considered obvious to combine two moieties used for the same purpose (MPEP 2144.06(I)); in this case, the tracheal administration of exogenous surfactant formulation with vascular administration of rhodamine. This is a combination of known elements (the administration of each formulation separately) yielding expected results (lower surface tension in the avelolar space).
Furthermore, it would be obvious to optimize the dose and dose schedule of the combination, to avoid unnecessary exposure of patients to subtherapeutic doses while preserving safety and maintaining rapid accrual, as discussed by Le Tourneau et al. As every drug and drug combination must have these parameters optimized, a person of skill in the art would reasonably be experienced in this optimization, leading to a reasonable expectation of success.
response to applicant’s arguments
Applicant references the arguments with respect to the rejection under 35 USC 103, above, which were answered there.
second rejection
Claims 44-47, 49, 50, and 61 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 19, and 22 of U.S. Patent No.9,693,990 in view of Le Tourneau et al (J. Natl. Cancer Inst. (2009) 101 p708-720).
Competing claim 1 describes a method of reducing ventilation injury (i.e. on a ventilator or will be placed on a ventilator) of a patient with aveolar flooding, comprising administering a rhodamine dye. Competing claim 19 specifies tracheal administration, while competing claim 22 specifies vascular administration.
The difference between the competing claims and the examined claims is that this reference does not discuss both vascular and airway administration together, nor does it discuss their timewise relationship.
Le Tourneau et al state that the main goal of the phase 1 clinical trial is to establish the dose and/or dose schedule for new drugs or drug combinations (abstract), to avoid unnecessary exposure of patients to subtherapeutic doses while preserving safety and maintaining rapid accrual (p708, 1st column, 2nd paragraph). A number of different experimental designs for establishing these numbers are mentioned (fig 2, p711, top of page). This reference discusses optimizing the dose schedule.
It is considered obvious to combine two moieties used for the same purpose (MPEP 2144.06(I)); in this case, the tracheal administration of exogenous surfactant formulation with vascular administration of rhodamine. This is a combination of known elements (the administration of each formulation separately) yielding expected results (lower surface tension in the avelolar space).
Furthermore, it would be obvious to optimize the dose and dose schedule of the combination, to avoid unnecessary exposure of patients to subtherapeutic doses while preserving safety and maintaining rapid accrual, as discussed by Le Tourneau et al. As every drug and drug combination must have these parameters optimized, a person of skill in the art would reasonably be experienced in this optimization, leading to a reasonable expectation of success.
response to applicant’s arguments
Applicant references the arguments with respect to the rejection under 35 USC 103, above, which were answered there.
third rejection
Claims 44-47, 49, 50, and 61 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, and 5 of U.S. Patent No. 9,504,796 in view of Le Tourneau et al (J. Natl. Cancer Inst. (2009) 101 p708-720).
Competing claim 1 describes a method of treating edema, comprising administering a rhodamine dye. Competing claim 2 specifies ventilator injury. Competing claim 4 specifies tracheal administration, while competing claim 5 specifies vascular administration.
The difference between the competing claims and the examined claims is that this reference does not discuss both vascular and airway administration together, nor does it discuss their timewise relationship.
Le Tourneau et al state that the main goal of the phase 1 clinical trial is to establish the dose and/or dose schedule for new drugs or drug combinations (abstract), to avoid unnecessary exposure of patients to subtherapeutic doses while preserving safety and maintaining rapid accrual (p708, 1st column, 2nd paragraph). A number of different experimental designs for establishing these numbers are mentioned (fig 2, p711, top of page). This reference discusses optimizing the dose schedule.
It is considered obvious to combine two moieties used for the same purpose (MPEP 2144.06(I)); in this case, the tracheal administration of exogenous surfactant formulation with vascular administration of rhodamine. This is a combination of known elements (the administration of each formulation separately) yielding expected results (lower surface tension in the avelolar space).
Furthermore, it would be obvious to optimize the dose and dose schedule of the combination, to avoid unnecessary exposure of patients to subtherapeutic doses while preserving safety and maintaining rapid accrual, as discussed by Le Tourneau et al. As every drug and drug combination must have these parameters optimized, a person of skill in the art would reasonably be experienced in this optimization, leading to a reasonable expectation of success.
response to applicant’s arguments
Applicant references the arguments with respect to the rejection under 35 USC 103, above, which were answered there.
Conclusion
THIS ACTION IS MADE FINAL. 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 FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
Examiner interviews are available via telephone 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, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658
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