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.
Priority
The instant application is a 371 of PCT/EP2021/059349 filed on 04/09/2021, and claims foreign priority to Netherlands application no. NL2025335 filed on 04/10/2020. The certified copy of the foreign priority application NL2025335 filed on 02/13/2023 is acknowledged.
Status of the Claims
The claim amendments and remarks filed on 01/28/2026 is acknowledged. Claims 1-2 and 12 are amended. Claims 4-5, 7-8, 11, and 13-18 are cancelled. Claims 19-23 are newly added.
Accordingly, claims 1-3, 6, 9-10, 12, and 19-23 are pending and being examined on the merits herein.
Withdrawn Rejections
The 35 USC 112(b) rejection for claims 1-3, 6, and 9-12 is withdrawn because claims 1-2 were previously unclear if the patient in the recited method must have all three of the previously recited conditions present, or if the recited method only required to be capable of treating each of these three recited conditions such that the subject does not necessarily require that all three conditions are present. Here, claims 1-2 now recite a method of treating only one condition and for recovery of one condition, which has changed the scope of the claims and requires further search and consideration.
The 35 USC 112(d) rejection for claim 11 is withdrawn in view of claim 11 being cancelled.
The 35 USC 103 rejection over Comper in view of Amici and Zuo for claims 2 and 11 are withdrawn because claim 2 was rejected based on meeting the limitation “for recovery of lung fibrosis”. However, amended claim 2 does not recite this limitation, which has changed the scope of the claim and requires further search and consideration. Additionally, claim 11 is cancelled, rendering the previous rejection moot.
The nonstatutory double patenting rejection over App No. ‘104 is withdrawn as this application is now abandoned.
The nonstatutory double patenting rejections over US’303 and App No. ‘137 for claims 2 and 11 are withdrawn because claim 2 was rejected based on meeting the limitation “for recovery of lung fibrosis”. However, amended claim 2 does not recite this limitation, which has changed the scope of the claim and requires further search and consideration. Additionally, claim 11 is cancelled, rendering the previous rejections moot.
The following grounds of rejection are maintained, amended, or new as necessitated by Applicant’s amendments.
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) 1-3, 6, 9-10, 12, and 20-22 are rejected under 35 U.S.C. 103 as being unpatentable over Comper et al. (WO2004093888A1 in PTO-892 dated 02/04/24) in view of Amici et al. (Antiviral Therapy, 2006 in PTO-892 dated 10/28/2025).
Comper et al. discloses methods for treating, preventing or managing coronavirus infections and/or viral infections including severe acute respiratory syndrome (SARS) in mammals using sulfated polysaccharides (see Abstract). Here, the SARS meets the limitation of a respiratory tract infection and lung disorder as recited in instant claims 20-21. Comper discloses that the terms "treat", "treating" and "treatment" refer to the eradication or amelioration of the infection itself, causes of the infection, or symptoms associated therewith, which meets the limitation of recovery of lung infection or lung disorder as recited in instant claims 2 and 22.
Comper et al. discloses that their compositions are useful as an antiviral against coronavirus infection, particularly respiratory infection or viral infection leading to respiratory disease (see paragraph 0007). Comper et al. discloses that the viral infection can include enveloped DNA or RNA viruses as well as positive-sense single-stranded RNA viruses (see paragraph 0011). Comper et al. discloses that “patient” or “subject” means an animal, preferably a mammal and most preferably a human (see paragraph 0015). Comper et al. discloses several sulfated polysaccharides that can be used in their methods including pentosan polysulfate preferably after their degree of sulfation is adjusted to treat or prevent coronavirus infections (see Table 1 in paragraph 0081). Comper et al. discloses that their compositions can be formulated as pharmaceutical compositions and dosage forms suitable for oral, mucosal (including sublingual, buccal, rectal, nasal, or vaginal), parenteral (including subcutaneous, intramuscular, bolus injection, intraarterial, or intravenous), transdermal, delivery via nebulizer, pulmonary delivery or topical administration (see paragraph 0084). Comper et al. discloses that suitable oral dosage forms include tablets, caplets, capsules, and liquids (see paragraph 0093). Comper et al. discloses that the oral dosage forms are prepared by mixing the active ingredients with liquid carriers or finely divide solid carriers (see paragraph 0093).
Comper et al. discloses that their compounds can be used in combination with at least one other therapeutic agent (see paragraph 0065). Comper et al. discloses that the other therapeutic agent can be an anti-inflammatory agent such as non-steroidal anti-inflammatory drugs (NSAIDs) including indomethacin and among others (see paragraph 0068). Comper et al. discloses that their sulfated compounds and the other therapeutic agents can act additively, or more preferably, synergistically (see paragraph 0075). Comper et al. discloses that the daily dosage amount is administered as single agents or in combination with other therapeutic agents (see paragraph 0063). Comper et al. discloses that the general dose per day for their administered sulfated compounds is in the range of 0.005-100 mg/kg as well as about 0.1mg-15 grams per day for the treatment of humans infected by coronavirus, (see paragraph 0063). Comper et al. further discloses that amounts sufficient to treat or prevent infections, but insufficient to cause, or sufficient to reduce, adverse effects associated with conventional therapies are also encompassed by the described dosage amounts and dose frequency schedules (see paragraph 0064), which is being interpreted as “administering a medicament in an effective amount for a sufficient period” as recited in claim 9.
The difference between Comper and the claimed invention is that Comper et al. does not disclose wherein pentosan polysulfate and the at least one compound are provided in a weight ratio of 1:1 to 10:1.
Amici discloses that indomethacin has a potent antiviral activity against SARS coronavirus (see Abstract). Amici demonstrates in Figure 3 on page 1026 that administering indomethacin at an oral dosage of 1 mg/kg bodyweight had a potent direct antiviral activity against canine coronavirus infected dogs. Amici also demonstrates the same antiviral effect when administering indomethacin to SARS-CoV infected vero cells in Figure 4 on page 1027. Amici further demonstrates the superior antiviral effect of indomethacin in comparison to another NSAID aspirin in Figures 5B and 5C on page 1028. Amici teaches that indomethacin does not affect coronavirus binding or entry into host cells, but acts by blocking viral RNA synthesis at cytoprotective doses (see Abstract). Amici teaches that this effect is independent of cyclooxygenase inhibition and concludes that indomethacin is a potent inhibitor of coronavirus replication and suggests that, having both anti-inflammatory and antiviral activity, indomethacin could be beneficial in SARS therapy (see Abstract).
It would have been prima facie obvious to combine Comper with Amici before the effective filing date of the claimed invention by selecting pentosan polysulfate and indomethacin as disclosed in Comper et al. with further guidance from Amici and further optimizing the disclosed dosages of the two compounds to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Comper discloses several combinations of polysulfated compounds and additional therapeutic agents including the combination of pentosan polysulfate with a NSAID which includes indomethacin. Furthermore, Amici provides further guidance that indomethacin is also useful for its anti-inflammatory and antiviral properties against the same coronavirus infections. Therefore, an ordinary skill artisan could have selected the combination of pentosan polysulfate and indomethacin in Comper with further guidance from Amici to yield predictable results. An ordinary skilled artisan would have a reasonable expectation of success because both Comper and Amici teach treating coronavirus infections using indomethacin as a therapeutic agent. Furthermore, Comper provides guidance of administering their polysulfated compounds at a dosage of 0.005 – 100 mg/kg, and Amici provides a dosage of 1 mg/kg indomethacin, therefore an ordinary skilled artisan could have performed routine optimization to arrive at the claimed weight ratio based on these disclosed dosages that would read on the recited weight ratio when combined. See MPEP 2144.05 II. Additionally, the disclosed dosages for polysulfated compounds and indomethacin suggests an overlapping ratio of pentosan polysuflate to indomethacin of 0.005:1 to 100:1 when combined, rendering the recited ratio obvious. See MPEP 2144.05 I.
In regards to instant claim 12, Comper provides guidance of administering their polysulfated compounds at a dosage of 0.005 – 100 mg/kg, and Amici provides a dosage of 1 mg/kg indomethacin, therefore an ordinary skilled artisan could have performed routine optimization to arrive at the recited dosage based on these disclosed dosages. See MPEP 2144.05. Additionally, the disclosed dosages for polysulfated compounds and indomethacin suggests an overlapping single dosage of pentosan polysuflate and indomethacin when combined, rendering the recited dosage obvious. See MPEP 2144.05 I.
Claim(s) 19 is rejected under 35 U.S.C. 103 as being unpatentable over Comper et al. (WO2004093888A1 in PTO-892 dated 02/04/24) in view of Amici et al. (Antiviral Therapy, 2006 in PTO-892 dated 10/28/2025), as applied to claim 1 above, and further in view of Finch et al. (US20110053986A1 in PTO-892).
The method of claim 1 is taught by the combined teachings of Comper and Amici as described above.
The combined teachings, however, do not disclose a combination of pentosan polysulfate and pioglitazone.
Finch discloses the use of the substantially pure 5R enantiomers of the known glitazone drug class, such as the known pharmaceutical products pioglitazone and rosiglitazone, for pulmonary administration by inhalation, for treatment of inflammatory respiratory diseases (paragraph 0001). Rinch discloses that the inhaled pulmonary administration of the 5R enantiomer of a glitazone, in particular the 5R-enantiomer of pioglitazone or rosiglitazone, allows the anti-inflammatory effect of the compound to be achieved more efficiently than by similar administration of the racemate, with all the concomitant reduced side effect benefits of lower systemic exposure than oral administration (paragraph 0018).
Finch discloses that their compositions are useful for treatment of several inflammatory respiratory disorders including infection due to coronavirus (including SARS) and among others (paragraph 0041).
It would have been prima facie obvious before the effective filing date of the claimed invention to have substituted the indomethacin as disclosed by the combined teachings of Comper and Amici described above with the 5R enantiomer of pioglitazone as disclosed in Finch to arrive at the claimed invention. One of ordinary skill in the art would have simply substituted one known element for another to obtain predictable results because the combined teachings of Comper and Amici described above teach a combination of pentosan polysulfate and anti-inflammatory agents for the treatment of coronavirus infections, and Finch also discloses that the 5R enantiomer of pioglitazone is useful as an anti-inflammatory agent for the treatment of coronavirus infection.
Claim(s) 23 is rejected under 35 U.S.C. 103 as being unpatentable over Comper et al. (WO2004093888A1 in PTO-892 dated 02/04/24) in view of Amici et al. (Antiviral Therapy, 2006 in PTO-892 dated 10/28/2025), as applied to claim 1 above, and further in view of Zuo et al. (Molecular Biology of the SARS-Coronavirus, 2009 in PTO-892 dated 07/03/2025).
The method of claim 1 is taught by the combined teachings of Comper and Amici as described above.
The difference between the combined teachings of Comper and Amici and the claimed invention is that the combined teachings of Comper and Amici do not disclose wherein the recited method is for recovery of lung fibrosis.
Zuo et al. discloses that severe acute respiratory syndrome (SARS) is an acute infectious disease with significant mortality, and that lung fibrosis is widely observed in patients who died from this disease (see Abstract and Conclusion on page 254). Zuo et al. discloses that lung fibrosis is a pathological consequence of acute and chronic interstitial lung disease (see page 249 first paragraph). Zuo et al. discloses coronavirus SARS (SARS-CoV) infection may lead to lung fibrosis through multiple signaling pathways and TGF-beta activation as one of the major contributors (see Abstract).
It would have been prima facie obvious to combine Comper and Amici with Zuo before the effective filing date of the claimed invention by further using the modified method based on the combined teachings of Comper and Amici described above for recovery of lung fibrosis in SARS patients as disclosed by Zuo. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Zuo provides guidance that lung fibrosis is common in patients with SARS-CoV, and the combined teachings of Comper and Amici provide a method of treating SARS associated coronavirus infections which can include the SARS-CoV patients described in Zuo. Therefore, an ordinary skilled artisan could have predictably applied the modified method of Comper and Amici to treat a SARS-CoV patient with lung fibrosis as disclosed in Zuo, and by treating this patient population, the recovery from lung fibrosis would naturally result from treatment and/or management of the SARS-CoV infection.
Response to Arguments
Applicant’s arguments filed on 01/28/2026 have been fully considered in so far as they apply to
the rejections of the instant office action, but were not persuasive.
Applicant states that Comper merely provides lists of twelve different classes of therapeutic compounds that may be optionally co-administered, and does not offer any rationale or data for co-administration. Applicant states the indomethacin disclosed in Comper is among over 100 options for co-administration, and further states that there is also no dosage, ratio, data, or guidance for this selection. Applicant states that Amici separately discloses administration of indomethacin at 1 mg/kg but does not disclose or suggest co-administration with pentosan polysulfate or any ratio between the two compounds. Applicant further states that Comper does not teach or suggest the use of pioglitazone.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Here, Comper teaches a finite number of additional agents including indomethacin for use in combination, any of which would reasonably expect to result in the predictable outcome of treating the coronavirus infection as discussed above. Furthermore, Amici provides additional guidance to select the indomethacin disclosed in Comper because Amici discloses that indomethacin is also useful for its anti-inflammatory and antiviral properties against the same coronavirus infections. Therefore, an ordinary skilled artisan, when viewing the combined teachings of Amici and Comper, could have predictably selected the combination of pentosan polysulfate and indomethacin with a reasonable expectation of success. Furthermore, the new rejection over Comper in view of Amici and Finch establishes obviousness for the combination of pentosan polysulfate and pioglitazone as described above.
Lastly, MPEP 2143.02 I states that “Conclusive proof of efficacy is not required to show a reasonable expectation of success … the expectation of success need only be reasonable, not absolute” and MPEP 2141.03(I) states that "A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR, 550 U.S. at 421, 82 USPQ2d at 1397. "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle."Id. at 420, 82 USPQ2d at 1397. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ."Id. at 418, 82 USPQ2d at 1396.”
Therefore, the combined teachings described above do not need to demonstrate the efficacy of the combination of pentosan polysulfate and indomethacin or pioglitazone as long as there is a reasonable expectation of success in the combination, and as described above, the combined teachings of Comper and Amici as well as Comper, Amici, and Finch provide this reasonable expectation of success.
Applicant states that the combined teachings of Comper and Amici define a broad ratio of ranges approximately 0.005:1 to 100:1. Applicant states that their claimed ratio of 1:1-10:1 constitutes a narrow and purposive range that is neither taught nor suggested by the cited references. Applicant states that the selection of this ratio range can only be achieved using impermissible hindsight. Applicant states that when the prior art does not recognize the parameter to be optimized as result-effective, optimization cannot render the claimed range obvious, and Applicant further states that neither Comper not Amici provide any guidance that would direct a skilled artisan toward any ratio.
Applicant’s arguments described above were not found persuasive because MPEP 2144.05 IIA states that “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation."
Here, it is within the skill of an ordinary person in the art to discover the optimum or workable ranges by routine optimization because while the combined teachings do not explicitly describe the recited weight ratios between the pentosan polysulfate and indomethacin, Comper provides guidance of combining pentosan polysulfate and indomethacin as described above. Furthermore, Comper provides guidance of administering their polysulfated compounds at an effective dosage of 0.005 – 100 mg/kg for treating SARS, and Amici also provides guidance of an effective dosage of 1 mg/kg indomethacin for treating SARS. Therefore, an ordinary artisan could have routinely optimized the dosages of the combination for treating SARS and could have, for example, selected a 1 mg/kg pentosan polysulfate dosage and a 1 mg/kg indomethacin dosage, which would be in a weight ratio of 1:1 and meet the recited weight ratio in the instant claims. The combined teachings of Comper and Amici do disclose a result-effective variable because the combined references teach an effective dosage for the recited pentosan polysulfate and indomethacin that can be co-administered to treat the same SARS condition.
Furthermore, it is noted that MPEP 2144.05 IIIA states that “Applicants can rebut a prima facie case of obviousness by showing the criticality of the range. "The law is replete with cases in which the difference between the claimed invention and the prior art is some range or other variable within the claims. . . . In such a situation, the applicant must show that the particular range is critical, generally by showing that the claimed range achieves unexpected results relative to the prior art range."
Here, Applicant has not demonstrated that the claimed narrower range of 1:1-10:1 is critical to rebut a prima facie case of obviousness over Comper in view of Amici because Applicant has not provided evidence that the claimed ranges achieve an unexpected result over the prior art ratio of approximately 0.005:1 to 100:1.
Applicant states that Comper shows in their multiple toxicity dose studies that the sulfated polysaccharide was administered to rats at dosages of 100 mg/kg up to 850 mg/kg with no apparent toxicity. Applicant states that although these studies were conducted in the context of tolerability assessment, Applicant states that they nevertheless represent a concrete dosing guidance and demonstrate that Comper directs a skilled artisan toward the use of very high dosages. Therefore, Applicant states that these exemplified dosages in Comper would represent ratios much higher than the claimed ratio of 1:1-10:1 and further states that this shows that Comper was focused on escalating polysaccharides dosages rather than balanced low-dose combinations with co-agents corresponding to the claimed ratio.
Applicant’s arguments described above were not found persuasive because MPEP 2123 II states that “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments.” Here, while Comper exemplifies higher dosages of the polysulfate polysaccharides, these examples do not teach away from the dosages of 0.005-100 mg/kg disclosed in Comper.
Applicant states that in regards to the recovery of lung fibrosis, the conclusion that fibrosis recovery would “naturally result” from the treatment disclosed by the combined teachings of Comper Amici, and Zuo is unsupported by the cited arts. Applicant further states the Zuo teaches that lung fibrosis “usually brings irreversible damage to the lung” and identifies as a future major challenge in the development of new therapies aimed at preventing SARS-CoV evoked lung fibrosis. Applicant states that surprisingly, their claim combination of pentosan polsyulfate and indomethacin potently reduces fibrosis based on the evidence provided in Figure 5. Applicant states that without motivation to combine Comper and Amici and in view of Zuo’s mentioned “major challenge”, an ordinary skilled artisan would not have reasonably expected that treatment of the SARS-CoV infection would result in recovery of lung fibrosis.
Applicant’s arguments described above were not found persuasive because MPEP 2145 II states that “Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention … Appellant argued that the presence of DEHP as the plasticizer in a blood collection bag unexpectedly suppressed hemolysis and therefore rebutted any prima facie showing of obviousness. However, the closest prior art utilizing a DEHP plasticized blood collection bag inherently achieved same result, although this fact was unknown in the prior art … The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious." Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter.m 1985) (The prior art taught combustion fluid analyzers which used labyrinth heaters to maintain the samples at a uniform temperature. Although appellant showed that an unexpectedly shorter response time was obtained when a labyrinth heater was employed, the Board held this advantage would flow naturally from following the suggestion of the prior art.). See also Lantech Inc. v. Kaufman Co. of Ohio Inc., 878 F.2d 1446, 12 USPQ2d 1076, 1077 (Fed. Cir. 1989), cert. denied, 493 U.S. 1058 (1990) (unpublished — not citable as precedent) ("The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.").”
Here, the instant specification discloses that the combination of these compounds at the recited ratio will result in recovery of lung fibrosis in a patient suffering from a DNA or RNA virus induced infections and disorders. While the prior art has not recognized this advantage of recovery of lung fibrosis, this result would flow naturally from the combined teachings of Comper, Amici, and Zuo because these combined teachings suggest administering the same combination of pentosan polysulfate and indomethacin at the recited weight ratios to treat the same patient populations that have SARS-CoV and lung fibrosis.
Furthermore, an explicit motivation disclosed in the art is not required in order to establish obviousness. MPEP 2141.03(I) recites "A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR, 550 U.S. at 421, 82 USPQ2d at 1397. "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle."Id. at 420, 82 USPQ2d at 1397. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ."Id. at 418, 82 USPQ2d at 1396.”
Lastly, in regards to Applicant’s showing of an unexpected result for the combination of pentosan polysulfate and indomethacin, Applicant has not provided sufficient evidence of an unexpected result to overcome the prima facie obviousness for the rejections described above for the following reasons below.
Here, Applicant has disclosed in the specification an experimental set-up of a fibrosis mouse model and administering different combinations/concentrations of the recited compounds, spilt into 7 different treatment groups as disclosed on page 9. The first treatment groups were given 4 mg/kg second compound, eg. indomethacin) and 40 mg/kg alternative/additional second compound alone along with DMSO/trapsol. The last treatment group was a control group given only DMSO/trapsol. The next four treatment groups were given various combinations of a first compound ranging from 20 or 50 mg/kg and either of the second compounds at 4 or 40 mg/kg. The instant specification states that the results show that the combinations provided a synergistic effect over the individually applied first and second compounds that were typically at least 2-20 times higher and that the fibrosis was largely or fully mitigated (page 10 lines 15-22).
However, the data/evidence supporting these synergistic results could not be found in the instant specification, making it difficult to ascertain which combinations as well as dosages has the synergistic result. It is noted that Applicant may file an appropriate affidavit or declaration to provide the evidence/data supporting the synergistic result for the claimed combinations as stated in MPEP 716.01(c).
Furthermore, as stated in MPEP 716.02(e), Applicant’s unexpected results must be compared to the closest prior art. Here, the closest prior art is Comper, which discloses combinations of pentosan polysulfate and anti-inflammatory agents such as non-steroidal anti-inflammatory drugs (NSAIDs) which includes indomethacin and others for the treatment of coronavirus infections and/or viral infections, and further states that these combinations can act additively or preferably synergistically (see paragraph 0075) as described above.
Applicant has not demonstrated an unexpected result over the combinations disclosed in Comper because Applicant has not provided the appropriate comparisons that are representative to Comper (ie, combinations of pentosan polysulfate and other NSAIDs), and Comper has further disclosed that their combinations can act synergistically. Furthermore, as described above, the data/evidence supporting the alleged synergistic results could not be found in the instant specification, making it difficult to ascertain which combinations as well as dosages has the alleged synergistic result.
Additionally, as described above, it is noted that MPEP 2144.05 IIIA states that “Applicants can rebut a prima facie case of obviousness by showing the criticality of the range. "The law is replete with cases in which the difference between the claimed invention and the prior art is some range or other variable within the claims. . . . In such a situation, the applicant must show that the particular range is critical, generally by showing that the claimed range achieves unexpected results relative to the prior art range."
Here, Applicant may overcome the obviousness rejections above by demonstrating the criticality of the claimed 1:1-10:1 ratio. However, as described above, Applicant has not demonstrated this criticality because Applicant has not provided evidence that the claimed narrower range achieves an unexpected result over the prior art ratio of approximately 0.005:1 to 100:1.
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.
Claims 1-3, 6, 9-10, 12, and 20-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of US 10,792,303 (‘303) in view of Comper et al. (WO2004093888A1 in PTO-892 dated 02/04/24) in view of Amici et al. (Antiviral Therapy, 2006 in PTO-892 dated 10/28/2025).
Claim 1 of ‘303 recites a pharmaceutical composition for use as a medicament for the inducement of beige/brite or brown fat tissue in vivo in the treatment of obesity or disorders contributed by obesity comprising a combination of active pharmaceutical ingredients consisting of: (ingredient i) a compound selected from at least one of Pentosan or polysulfated glycosaminoglycan in combination with (ingredient ii) at least one non-protein or non-nucleic acid compound, different from (ingredient i), that can activate PPAR, wherein (ingredient ii) is a PPARγ agonist selected from triglitazone, rosiglitazone, ciglitazone, pioglitazone, or indomethacin. Claim 3 of ‘303 wherein the composition further comprises at least one pharmaceutically acceptable carrier. Claims 4-5 of ‘303 recite wherein the ingredients are combined in one dosage form or separate dosage forms. Claims 6-7 of ‘303 recite the composition is suitable for oral administration and in a form a tablet or capsule. Claim 11 of ‘303 recites wherein the patient is a pet or mammal.
The difference between the claims of ‘303 and the claimed invention is that the claims of ‘303 do not recite a method of treating enveloped DNA or RNA virus induced infections and disorders.
The independent teachings of Comper et al. and Amici et al. are as described above.
It would have been prima facie obvious to combine the claims of ‘303 with Comper and Amici before the effective filing date of the claimed invention by administering the composition recited in the claims of ‘303 for treating enveloped DNA or RNA virus induced infections and disorders as disclosed in Comper with further guidance from Amici. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Comper provides guidance that the same combination of the two compounds recited in the claims of ‘303 can also be used to treat enveloped DNA or RNA virus induced infections and disorders, and Amici provides further guidance that indomethacin is also useful for its anti-inflammatory and antiviral properties against the same coronavirus infections. Therefore, an ordinary skill artisan could have predictably used the recited combination of pentosan polysulfate and indomethacin treat enveloped DNA or RNA virus induced infections and disorders based on the combined teachings of Comper and Amici with a reasonable expectation of success. Furthermore, Comper provides guidance of administering their polysulfated compounds at a dosage of 0.005 – 100 mg/kg, and Amici provides a dosage of 1 mg/kg indomethacin. Therefore, an ordinary skilled artisan could have performed routine optimization to arrive at the claimed weight ratio based on these disclosed dosages that would read on the recited weight ratio when combined. See MPEP 2144.05 II.
In regards to instant claim 12, it would have also been prima facie obvious to optimize the mg/kg dosage of the two recited compounds to be 1-10 mg/kg in one dosage form for the modified method from the combination of the claims of ‘303 and the teachings of Comper and Amici described above. One of ordinary skill in the art would have been able to perform routine optimization based on Comper administering their polysulfated compounds at a dosage of 0.005 – 100 mg/kg, and Amici providing a dosage of 1 mg/kg indomethacin. See MPEP 2144.05 II.
Claims 1 and 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of US 10,792,303 (‘303) in view of Comper et al. (WO2004093888A1 in PTO-892 dated 02/04/24), Amici et al. (Antiviral Therapy, 2006 in PTO-892 dated 10/28/2025), and Finch et al. (US20110053986A1 in PTO-892).
The combination of the claims of ‘303, Comper, and Amici recite the method of instant claim 1 as described above.
The combination, however, does not recite a combination of pentosan polysulfate and pioglitazone for the treatment of enveloped DNA or RNA virus induced infections and disorders.
The teachings of Finch are as described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have substituted the indomethacin as recited by the combination of the claims of ‘303, Comper, and Amici described above with the 5R enantiomer of pioglitazone as disclosed in Finch to arrive at the claimed invention. One of ordinary skill in the art would have simply substituted one known element for another to obtain predictable results because the combination of the claims of ‘303, Comper, and Amici described above recite a combination of pentosan polysulfate and anti-inflammatory agents for the treatment of coronavirus infections, and Finch also discloses that the 5R enantiomer of pioglitazone is useful as an anti-inflammatory agent for the treatment of coronavirus infection.
Claims 1 and 23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of US 10,792,303 (‘303) in view of Comper et al. (WO2004093888A1 in PTO-892 dated 02/04/24), Amici et al. (Antiviral Therapy, 2006 in PTO-892 dated 10/28/2025), and Zuo et al. (Molecular Biology of the SARS-Coronavirus, 2009 in PTO-892 dated 07/03/2025).
The method of instant claim 1 is taught by the combination of the claims of ‘303, Comper, and Amici as discussed above.
The described combination, however, does not recite wherein the method is for recovery of lung fibrosis or treating fibrosis.
The teachings of Zuo are as described above.
It would have been prima facie obvious to combine the claims of ‘303, Comper, and Amici with Zuo before the effective filing date of the claimed invention by further using the combined method of the claims of ‘303, Comper, and Amici as described above for recovery of lung fibrosis and/or treating fibrosis in SARS patients as disclosed by Zuo. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Zuo provides guidance that lung fibrosis is common in patients with SARS-CoV, and the combined method of the claims of ‘303, Comper, and Amici as described above provides a method of treating SARS associated coronavirus infections which can include the SARS-CoV patients described in Zuo. Therefore, an ordinary skilled artisan could have predictably applied this modified method to treat a SARS-CoV patient with lung fibrosis as disclosed in Zuo, and by treating this patient population, the recovery from lung fibrosis would naturally result from treatment and/or management of the SARS-CoV infection.
Claims 1-3, 6, 9-10, 12, and 20-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 and 14-19 of copending Application No. 18/571,137 (‘137) in view of Comper et al. (WO2004093888A1 in PTO-892 dated 02/04/24) in view of Amici et al. (Antiviral Therapy, 2006 in PTO-892 dated 10/28/2025).
The claims of ‘137 recites the same pharmaceutical composition of the instant application comprising one compound such as pentosan polysulfate (claim 9) and another compound such as indomethacin (claim 10) in a weight ratio of 1:1 to 10:1 (claim 19). The claims of ‘137 also recite the same dosage form of a tablet (claim 17) and sub-cutaneous application (claim 18). Furthermore, the claims of ‘137 recite overlapping ranges such as 0.001-10mg active ingredients/kg body weight (claim 16), 20-100 mg active ingredient per dosage (claim 18), and total weight of active ingredients from 1-100 mg per dosage (claim 19). The claims of ‘137 also recite further comprising at least one pharmaceutically acceptable carrier.
The difference between the claims of ‘137 and the claimed invention is that the claims of ‘137 do not recite a method of treating enveloped DNA or RNA virus induced infections and disorders.
The independent teachings of Comper et al. and Amici et al. are as described above.
It would have been prima facie obvious to combine the claims of ‘137 with Comper and Amici before the effective filing date of the claimed invention by administering the composition recited in the claims of ‘137 for treating enveloped DNA or RNA virus induced infections and disorders as disclosed in Comper with further guidance from Amici. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Comper provides guidance that the same combination of the two compounds recited in the claims of ‘137 can also be used to treat enveloped DNA or RNA virus induced infections and disorders, and Amici provides further guidance that indomethacin is also useful for its anti-inflammatory and antiviral properties against the same coronavirus infections. Therefore, an ordinary skill artisan could have predictably used the recited combination of pentosan polysulfate and indomethacin treat enveloped DNA or RNA virus induced infections and disorders based on the combined teachings of Comper and Amici with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Claims 1 and 19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 and 14-19 of copending Application No. 18/571,137 (‘137) in view of Comper et al. (WO2004093888A1 in PTO-892 dated 02/04/24), Amici et al. (Antiviral Therapy, 2006 in PTO-892 dated 10/28/2025), and Finch et al. (US20110053986A1 in PTO-892).
The combination of the claims of ‘137, Comper, and Amici recite the method of instant claim 1 as described above.
The combination, however, does not recite a combination of pentosan polysulfate and pioglitazone for the treatment of enveloped DNA or RNA virus induced infections and disorders.
The teachings of Finch are as described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have substituted the indomethacin as recited in the combination of the claims of ‘137, Comper, and Amici described above with the 5R enantiomer of pioglitazone as disclosed in Finch to arrive at the claimed invention. One of ordinary skill in the art would have simply substituted one known element for another to obtain predictable results because the combination of the claims of ‘137, Comper, and Amici described above recite a combination of pentosan polysulfate and anti-inflammatory agents for the treatment of coronavirus infections, and Finch also discloses that the 5R enantiomer of pioglitazone is useful as an anti-inflammatory agent for the treatment of coronavirus infection.
This is a provisional nonstatutory double patenting rejection.
Claims 1 and 23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 and 14-19 of copending Application No. 18/571,137 (‘137) in view of Comper et al. (WO2004093888A1 in PTO-892 dated 02/04/24), Amici et al. (Antiviral Therapy, 2006 in PTO-892 dated 10/28/2025), and Zuo et al. (Molecular Biology of the SARS-Coronavirus, 2009 in PTO-892 dated 07/03/2025).
The method of instant claim 1 is taught by the combination of the claims of ‘137, Comper, and Amici as discussed above.
The described combination, however, does not recite wherein the method is for recovery of lung fibrosis or treating fibrosis.
The teachings of Zuo are as described above.
It would have been prima facie obvious to combine the claims of ‘137, Comper, and Amici with Zuo before the effective filing date of the claimed invention by further using the combined method of the claims of ‘137, Comper, and Amici as described above for recovery of lung fibrosis and/or treating fibrosis in SARS patients as disclosed by Zuo. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Zuo provides guidance that lung fibrosis is common in patients with SARS-CoV, and the combined method of the claims of ‘137, Comper, and Amici. as described above provides a method of treating SARS associated coronavirus infections which can include the SARS-CoV patients described in Zuo. Therefore, an ordinary skilled artisan could have predictably applied this modified method to treat a SARS-CoV patient with lung fibrosis as disclosed in Zuo, and by treating this patient population, the recovery from lung fibrosis would naturally result from treatment and/or management of the SARS-CoV infection.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant defers addressing the double patenting rejections until they are the only rejections remaining. Therefore, the double patenting rejections over US’303 and ‘137 are maintained.
Conclusion
No claim is found allowable.
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.
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/D.H.C./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693
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