DETAILED ACTION
This office action is in response to the Applicant’s filing dated February 4th, 2026.
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 .
Status of Claims
Claims 11-15, 18, 26 and 47-49 are pending in the instant application. Acknowledgement is made of Applicant’s remarks and amendments filed on February 4th, 2026. Acknowledgment is made of Applicant’s amendment of claims 11-13, 15 and 18; and the cancelation of claims 1-10, 16-17, 19-25 and 27-46.
Claims 26 and 47-49 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected group, there being no allowable generic or linking claim. Claims 11-15 and 18 are presently under examination as they relate to the elected invention.
Objections and/or Rejections and Response to Arguments
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated (Maintained Objections and/or Rejections) or newly applied (New Objections and/or Rejections, Necessitated by Amendment or New Objections and/or Rejections, NOT Necessitated by Amendment). They constitute the complete set presently being applied to the instant application.
New Objections and/or Rejections
Necessitated by Claim Amendment
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.
Claims 11-15 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Pearson et al (WO 2005/063732 A1), cited in a previous Office action; in view of Emaleh et al (WO 2020/051322 A1); further in view of NIH.gov (https://www.nih.gov/news-events/news-releases/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19), cited in a previous Office action; further in view of Aljuffali et al (Expert Opinion on Drug Delivery, (2016); 13(9), 1311-1325), cited in a previous Office action.
Regarding claims 11-15 and 18, Pearson teaches a compound combination agent (codrug) for treating a pulmonary disorder, such as asthma, represented by the structure
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; wherein the linker can be represented by the -C(O)NH- structure
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in which A1 is a mast cell stabilizer having a carboxylic acid substituent and B1 is an iNOS inhibitor (page 5, paragraph [0013]). Pearson teaches a mast cell stabilizer moiety of Formula I known as Cromolyn shown below:
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wherein R1 is -NHR6, and -NHR6 is a deshydrogen residue of an amine, the parent of which (R6NH2) is an iNOs inhibiting moiety; wherein R2 is hydroxy (it is noted R1 can also be hydroxy); and wherein R3 is H (page 1, paragraphs [0001-0003]; pages 3-7, paragraphs [0008-0009, 0014]). Cromolyn is a compound of instantly claimed Formula (I) wherein R1 is OH; wherein R2 and R3 are CO2R4 and R4 is H; wherein at the R2 position an amine has formed a labile bond to create a codrug. Pearson teaches that Cromolyn is known to have poor bioavailability alone, with 8% absorption via inhalation and 1% absorption orally (page 1, paragraph [0003]).
Pearson does not teach fluorine modified Cromolyn bound to a residue of Remdesivir, thereby forming a codrug.
Emaleh teaches the fluorine modified cromolyn molecule shown below (page 25, third compound):
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Emaleh teaches this molecule is useful for treating viral infections, including ebola and avian influenza, as well as Cytokine Release Syndrome (CRS) and Acute Respiratory Distress Syndrome (ARDS) (pages 37-38, claims 1, 2, 6, 9 and 16). ARDS and CRS are inflammatory pulmonary conditions associated with severe viral infections, including Ebola, avian influenza and COVID-19. Thus, Emaleh expressly teaches fluorination of cromolyn at the instantly claimed R1 position in the context of treating viral pulmonary conditions.
NIH.gov teaches that Remdesivir, shown below:
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was administered to patients with COVID-19, a severe viral pulmonary disorder, and led to a 31% faster time to recovery than placebo; with a median time to recovery of 11 days for patients treated with Remdesivir, compared to 15 days for patients who received placebo. The Remdesivir group also benefited from an improved mortality rate of 8.0%, as opposed to 11.6% for the placebo group (page 1, last paragraph; page 2, first paragraph). It is noted that the chemical structure of Remdesivir contains a primary amine group.
Aljuffali teaches that the conjugation of two drugs into a codrug can increase the therapeutic effect, when compared to the parent compounds individually (page 1312, right column, second paragraph). Aljuffali further teaches that in comparison to the individual parent compounds, codrugs benefit from increased absorption, short lag time, increased bioavailability, a reduced toxicity and a synergistic effect on drug therapy (page 1313, left column, paragraphs 3-5).
It would have been prima facie obvious to a person of ordinary skill in the art to combine the Remdesivir antiviral compound used to treat pulmonary disorders, such as COVID-19, and improve patient outcomes as taught by NIH.gov, with Cromolyn of Pearson used to treat pulmonary disorders; fluorine modified at the instantly claimed R1 position of Cromolyn as taught by Emaleh is therapeutically useful to treat viral pulmonary disorders, the thereby arriving at the instantly claimed fluorinated cromolyn-Remdesivir codrug. Chemically, this would be a predictable substitution of one known primary amine bearing therapeutic agent for another, maintaining the same functional codrug linkage taught by Pearson, while incorporating the fluorine modification of cromolyn expressly taught by Emaleh with the same therapeutic intent of treating a viral pulmonary disorder. This conjugation aligns with Aljuffali’s teachings that codrugs exhibit improved pharmacokinetic properties and synergistic effects relative to the individual parent compounds. One of ordinary skill in the art would have reasonably expected that such conjugation would have maintained baseline therapeutic effect of the parent drugs, while potentially having a synergistic therapeutic effect, and improving their overall pharmacokinetic profile. Ultimately, this conjugation represents a routine optimization of known therapeutic strategies with predictable results.
“[T]he rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395.
Applicant argues:
None of Pearson, NIH.gov or Aljuffali teach or suggest introduction of a halogen at the instantly claimed R1 position of cromolyn.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
While Pearson does not explicitly teach or suggest a halogen at the instantly claimed R1 position, modifications at that position, described as variable R3 in Formula (I) of Pearson (page 4, paragraph [0009]), are disclosed to vary biological activity and pharmacological properties. One ordinary skill in the art would have recognized this position to tolerate substitution for purposes of modulating activity or physicochemical properties.
Emaleh expressly teaches cromolyn derivatives fluorinated at the instantly claimed R1 position, and that it is useful in treating viral pulmonary conditions (see above rejection). Emaleh therefore provides clear motivation to introduce a fluorine substituent into cromolyn at the position indicated as being a site for routine structural modification and optimization in Pearson, used in the same therapeutic context. Thus, the introduction of fluorine at the instantly claimed R1 position represents a predictable structural modification expressly taught in the art.
“[T]he rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395.
Conclusion
Claims 11-15 and 18 are rejected.
No claim is allowed.
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 CHRISTOPHER L JOHNSON whose telephone number is (571)272-1672. The examiner can normally be reached Monday - Friday 08:00AM - 5:00PM EST with Flex on Fridays.
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/C.L.J./Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
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