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 .
Claims 4-8, 11-24, and 27 are cancelled.
Claims 1-3, 9-10, and 25-26 are pending and under examination on the merits.
Withdrawn Claim Objections and Rejections
The objections to claims 1 and 3 are withdrawn in light of the corrective claim amendments dated 03/13/2026. The rejections of claims 16-18 under 35 USC §103 are withdrawn as moot in light of the cancellation of the claims resulting from the 03/13/2026 claim amendments.
Maintained-Claim Interpretation
Recitations of treating a viral infection are being interpreted to mean that said treatment is a reduction in one or more of pulmonary inflammation, lung damage, decreased pulmonary neuroendocrine cells (PNECs), GRP gene expression, GRP protein production, GRPR activation, GRPR signaling, inflammatory cytokine and/or chemokine production, and HMGB1 release in the subject in comparison to a subject infected with the virus but not receiving treatment (as is consistent with the specification (see for example paragraph 16)).
Maintained-Claim Rejections
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.
Claims 1-3, 9-10, and 25-26 are rejected under 35 U.S.C. 103 as being unpatentable over Shirey et al (The TLR4 antagonist Eritoran protects mice from lethal influenza infection. Nature 497, 498–502 (2013). https://doi.org/10.1038/nature12118) in view of Petronilho et al (Gastrin-releasing peptide receptor antagonist induces a protection from lethal sepsis: involvement of toll-like receptor 4 signaling. Crit Care 14 (Suppl 2), P46 (2010). https://doi.org/10.1186/cc9149), and Moody et al (BW2258U89: A GRP receptor antagonist which inhibits small cell lung cancer growth, https://doi.org/10.1016/0024-3205(94)00481-7, as cited in the 03/09/2021 IDS)).
Shirey et al teach an investigation of alternatives to annual influenza vaccines using murine models. Shirey et al teach that therapeutic administration of Eritoran (also known as E5564)—a potent, well-tolerated, synthetic TLR4 antagonist, blocks influenza-induced lethality in mice, as well as lung pathology (where acute lung injury is secondary to TLR4-dependent inflammation), and thus represents a novel therapeutic approach for inflammation associated with influenza (see for example the abstract).
Shirey et al do not teach administration of a GRPR antagonist to a subject with influenza.
However, Petronilho et al explore the role of GRPR antagonism in TLR4-related lethal sepsis using in vitro and in vivo (rat and human subjects) methods. Petronilho et al teach that treatment with RC-3095, a selective gastrin-releasing peptide receptor (GRPR) antagonist, decreased lung TLR-4 content, reduced the migration of inflammatory cells to the lung (thereby reducing the number of infiltrating inflammatory cells as recited in instant claim 3), and reduced systemic cytokine levels (see the abstract at the results sub-section, at the left-hand column of pg. S20).
Petronilho et al do not explicitly teach the use of the BW2258U89 GRPR antagonist.
However, Moody et al teach the use of the BW2258U89 GRPR antagonist to inhibit small cell lung cancer (SCLC) growth in a xenograft of nude mice. Moody et al teach that BW2258U89 is a known GRPR antagonist with known activity in the lung (treatment of SCLC).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of Shirey et al, Petronilho et al, and Moody et al. The artisan would have been motivated to make and use the invention as claimed because Shirey et al teach that subjects with influenza may experience acute lung injury as a result of TLR4 activity which is dependent upon activity of GRPR, as taught by Petronilho et al (see for example pages S19-S20). One of ordinary skill in the art would have found it obvious to use the BW2258U89 antagonist of Moody et al in place of the antagonist taught by Petronilho et al because it is prima facie obvious to swap one known equivalent for another to achieve the same purpose, here, to swap one known GRPR antagonist for another, as functional equivalents (see MPEP sections 2143(I)(B) and 2144.06 (II)). The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Regarding claim 2, where the structures taught are the same (noting the prior art antagonist of Moody et al is the instantly claimed antagonist) and the active steps (administering the antagonist) are made obvious to practice in the same population (a subject infected with influenza), the effects/results of practicing the method are presumed to occur because function flows from structure. Here, administration of the claimed antagonist is presumed to evoke the claimed result of reducing GRP-induced lung pathology. Note further, GRP signaling is dependent upon GRPR such that antagonism of GRPR would have been logically understood to reduce any effects caused by GRP activity, such as those claimed. Further note that the effects taught by the prior art (such as reducing the infiltration/migration of inflammatory cells into the lung; see for example pages S19-S20 of Petronilho et al) would have further been understood by one of ordinary skill in the art to reflect or result in a reduction of GRP-induced lung pathology).
Regarding claim 3, where the structures taught are the same (noting the prior art antagonist of Moody et al is the instantly claimed antagonist) and the active steps (administering the antagonist) are made obvious to practice in the same population (a subject infected with influenza), the effects/results of practicing the method are presumed to occur because function flows from structure. Here, administration of the claimed antagonist is presumed to effect the claimed result of reducing GRP-induced lung pathology, where said pathology is one or more of increased numbers of mononuclear cell masses surrounding conducting airways, increased numbers of neutrophil masses in alveoli, increased numbers of PNEC, degradation of airway parenchyma at bronchiole/alveoli foci due, for example, to infiltrating inflammatory cells; breakdown of pulmonary capillary integrity, and leaky vasculature. For the reasons iterated in the rejection of claim1, above, the method of administering the antagonist as claimed would have been obvious. The MPEP provides that:
"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel." Id. See also MPEP 2112(I) with regard to inherency and product-by-process claims and MPEP § 2141.02 with regard to inherency and rejections under 35 U.S.C. 103,”
(see MPEP 2112(I)). Thereby, the cited references (in their entirety) and teachings are held to make obvious administration of the claimed antagonist to a subject infected with influenza.
Regarding 9-10, as discussed above, Petronilho et al teach administration of a GRPR antagonist at a concentration which decreased TLR4 and, as a result, reduced the migration of inflammatory cells to the lung and reduced systemic cytokine levels (see the abstract at the results sub-section, at the left-hand column of pg. S20). Therefore, Petronilho et al teach administration of a GRPR antagonist at a therapeutically effective dose. Note that this amount is presumed to result in at least the therapeutic effects of reduced lung damage/inflammation, reduced inflammatory cytokine production (through reduced levels), and potentially other recited effects given that function flows from structure and the compounds and active steps of claims 1-3 and 9-10 are identical with those of the combined cited prior art references.
Regarding claims 25-26, Shirey et al teach that reduced TLR4 activity (accomplished by TLR4 antagonism) is accomplished in influenza A, specifically and H1N1 strain (influenza virus (A/PR/8/34); non-adapted 2009 human pandemic influenza strain A/California/07/2009H1N1) (see for example pages 498-499 and the methods section of page 503). Therefore, the method resulting from the prior art references, made obvious for reasons stated above, would have been understood to function predictably in influenza A, H1N1 subtype influenza by one of ordinary skill in the art, with a reasonable expectation of success.
Applicants Arguments and Reponses
A. Applicant argues for withdrawal of the rejections under 35 USC §103. Applicant argues that the Shirey reference in isolation does not teach the totality of claim 1 (see page 5 of the 03/13/2026 remarks). Applicant argues that the Petronilho reference in isolation does not teach the totality of claim 1 (see page 6 of the 03/13/2026 remarks). Applicant argues that the combination of Shirey et al and Petronilho et al do not make obvious administration of a GRPR antagonist for treating GRP-induced pulmonary inflammation in a subject infected with an influenza virus and points to differences between the references (predominantly, the difference between influenza and carrageenan) (see page 6 of the 03/13/2026 remarks). Applicant argues that not all GRPR antagonists act exactly the same and that factors such as dosing/concentration may differ among different antagonists and points out that to date, the BW2258U89 antagonist has only been tested and shown efficacious for treating neuroendocrine tumors such that there would be no reasonable expectation of success in administering BW2258U89 in the method resulting from the combination of Shirey et al and Petronilho et al according to Moody et al (see pages 6-7 of the 03/13/2026 remarks).
Response: 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). Applicant’s focus on the different between influenza and carrageenan ignores the cited mechanistic teachings clearly motivating the artisan to administer a GRPR antagonist to a subject with influenza and GRP-induced pulmonary inflammation. Shirey et al establish that pulmonary inflammation in the setting of sepsis occurs in a TLR-4 driven manner. Petronilho et al explore the role of GRPR antagonism in TLR4-related lethal sepsis using in vitro and in vivo (rat and human subjects) methods. Petronilho et al teach that treatment with RC-3095, a selective gastrin-releasing peptide receptor (GRPR) antagonist, decreased lung TLR-4 content, reduced the migration of inflammatory cells to the lungs, and reduced systemic cytokine levels, which that artisan would have understood to be indications of ameliorating pulmonary inflammation. Even though influenza and carrageenan are different, this GRP/TLR4 mechanism for pulmonary inflammation is taught to be the same by the art. The art motivates treating pulmonary inflammation in any disease where GRP/TLR4 is mechanistically understood to drive pulmonary inflammation by administering a GRPR antagonist. Regarding the unpredictability of using the claimed antagonist as a functional equivalent, the arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). See MPEP 2145 (I). There is nothing in the art to suggest unpredictability with using the antagonist of Moody et al in place of the antagonist of Petronilho et al. Furthermore, the question of interest for patentability is not whether something has been previously shown safe and effective, but is whether the state of the prior art would have motivated the artisan to arrive at the claimed invention prior to the effective filing date. Here, the artisan would have been so motivated without specific validation of safety and efficacy. The inventive impulse often motivates testing of safety and efficacy. The required reasonable expectation of success does not require an absolute removal of any uncertainty as by prior proof of success, but merely requires “the likelihood of success” in combining or modifying prior art disclosures to meet the limitations of the claimed invention. See Elekta Ltd. v. ZAP Surgical Sys., Inc., 81 F.4th 1368, 1375, 2023 USPQ2d 1100 (Fed. Cir. 2023) and Intelligent Bio-Sys., Inc. v. Illumina Cambridge Ltd., 821 F.3d 1359, 1367, 119 USPQ2d 1171, 1176 (Fed. Cir. 2016) (see MPEP §2143.02). Here, there was reason to believe there was a likelihood of success based on the prior art reference as combined in the rejections of record. These arguments are unpersuasive. Therefore, the rejections of record are maintained at this time.
Conclusion
No claim is allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Petronilho et al (Protective effect of gastrin-releasing peptide receptor antagonist in carrageenan-induced pleural inflammation in rats. Inflamm. Res. 59, 783–789 (2010). https://doi.org/10.1007/s00011-010-0190-8) teach that RC-3095 exhibited pronounced anti-inflammatory actions by inhibition of leukocyte influx and blockade of MPO, nitrite/nitrate and cytokine levels.
Qin et al (Current Opinion in Endocrinology & Diabetes and Obesity 20(1):p 22-26, February 2013. | DOI: 10.1097/MED.0b013e32835bc368) teach that gastrin-releasing peptide (GRP) was involved in the airway inflammation in murine models of airway hyperreactivity.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ASHLEY GAO whose telephone number is (571) 272-5695. The examiner can normally be reached on Monday- Friday 8-5pm.
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.
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/Ashley Gao/
Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
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