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 .
Election/Restrictions
Applicant’s election of the species of cilengitide and a coronavirus comprising an RGD domain in the receptor binding domain of the spike protein (SARS-CoV-2) in the reply filed on 2/25/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim Status
Claims 1-12, 14, and 16 are pending under examination and are currently amended. Claims 13 and 15 are cancelled.
Priority
The instant application is the 371 national stage entry of PCT/EP2022/051399, filed 1/21/2022, which claims priority to EP21153061.3, filed 1/22/2021. The priority date of 1/22/2021 is acknowledged.
Information Disclosure Statement
The IDS filed 7/20/2023 is under consideration.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see Pg 10, line 33, and Pg 22, line 9). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of the term PyMol (Pg 27, last line), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 5, 9, and 11 are objected to because of the following informalities
Claim 5 recites “the functional variant thereof, is administered at a dosage”. Remove the comma between “thereof” and “is” for improved readability.
Claim 9 recites “the functional variant thereof administered as a composition”. Add the word “is” between “thereof” and “administered” such that the claim reads “the functional variant thereof is administered as a composition” for improved readability.
Claim 11 recites “is administered by for oral administration”. Amend the claim such that it either recites “by oral administration” or “for oral administration” for improved readability.
Appropriate correction is required.
Claim Interpretation
Claims 1, 8, and 14 each recite a method of treatment or prevention, where the active step is administration of cilengitide or a functional variant thereof. The instant specification defines prevention as preventing or delaying the onset or progression of a disease, synonymous with prophylaxis (see instant Pg 13, lines 18-23). Prevention as recited in each of these claims is being interpreted as occurring in a subject who does not yet have the condition recited in the preamble (i.e., a coronavirus infection, a cardiovascular dysfunction or effect associated with coronavirus infection, or loss of barrier function associated with coronavirus infection).
Claim 2 recites the coronavirus is one comprising an RGD domain in the receptor binding domain of the spike protein. Per the instant specification, SARS-CoV-2 has such a mutation (see instant Pg 3, lines 10-15; Figure 2). As such, this claim is being interpreted as the coronavirus is SARS-CoV-2.
Claim 4 recites that the cilengitide or a functional variant thereof binds to αVβ3 integrin on vascular endothelial cells. This limitation describes a functional rather than a structural element of the instant invention. As such, the claim is being interpreted based upon the structural limitation recited in base claim 1 (administering cilengitide or a functional variant thereof), where the functional limitation is a property endowed by the structure.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 7 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 7 recites that the method of claim 1 is used for early treatment or prevention of loss of barrier function associated with the infection. The instant specification indicates that binding of SARS-CoV-2 to endothelial cells is associated with loss of barrier function (see instant Pg 9, lines 20-21). In other words, loss of barrier function is a component of a SARS-CoV-2 infection, and early treatment or prevention would be encapsulated by treatment or prevention as recited in claim 1. Therefore, claim 7 does not further limit claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
First rejection – written description
Claims 1-12, 14, and 16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are drawn to methods of treatment or prevention of a coronavirus infection, cardiovascular dysfunction or effect associated with coronavirus infection, or loss of barrier function associated with coronavirus infection, through administration of cilengitide or a functional variant thereof. The instant specification teaches that functional variants of cilengitide means the variants of cilengitide as described in US6001961, which are SEQ ID NO: 1-40 and inhibitors of integrin αVβ3. Additionally, the instant specification notes that a functional variant has the same function e.g., a variant of cilengitide which differs by a modification but maintains the same function, i.e. integrin inhibitor. Typically, the functional variant of cilengitide is acyclic peptide comprising an RGD sequence or motif (Pg 16, lines 13-18). Beyond this, the instant specification does not provide any examples of peptide sequences that constitute functional variants.
The limitation “a functional variant thereof” does not disclose sufficient structure-function relationship to meet the written description requirement. As stated above, the claims require that a functional variant of cilengitide retain the same function but differ structurally from cilengitide itself; more specifically, in claim 4, the functional variant should be able to bind to αVβ3. However, beyond being cyclic in nature and comprising an RGD motif, the claims do not indicate structural information.
Kelly et al. (US 20060058228, published 3/16/2006) discuss a phage display screen to identify peptides that distinguish between well-differentiated (HCT116) and poorly-differentiated (HT29) colon cancer cell lines. Analysis of the selected library resulted in the identification of a nine amino acid, disulfide-constrained peptide having a three amino acid (arg-pro-met, “RPM”) motif that specifically binds HT29 cells ([0032]). Substituting each of RPM with alanine significantly limited or abolished the ability of the peptide to compete with wild type RPM in a binding assay, indicating that these three residues alone accounted for the ability to bind to HT29 cells ([0034]). In contrast to this example, it is unknown which structural features of cilengitide must be retained to maintain its αVβ3 binding function, and one cannot extrapolate how even a few residue changes might impact functionality.
Further, Guo (H.H. Guo, J. Choe, & L.A. Loeb, Protein tolerance to random amino acid change, Proc. Natl. Acad. Sci. U.S.A. 101 (25) 9205-9210, (2004).) teaches that a protein’s tolerance to random substitutions ultimately depends on whether the residues at hand are involved the protein’s functional activity. For instance, regions that were highly substitutable in the human DNA repair enzyme 3-methyladenine DNA glycosylase (AAG) include the first 79 N-terminal residues previously demonstrated to be unnecessary for in vitro enzyme activity and DNA binding specificity. In contrast, residues that are involved in glycosylase function or DNA binding did not tolerate amino acid substitutions (“Substitutability and Structure”, Pg 9207-9209; Figure 1). Figure 1 of Guo also indicates that tolerated substitutions are generally conservative, i.e., a nonpolar residue is substituted for another nonpolar residue, etc. However, there are no explicit limitations in the instant claims regarding the structural features that should be retained in a cilengitide functional variant as compared to those that can be modified in the above listed claims.
Consequently, one skilled in the art could not possibly know the structural features of a functional variant of cilengitide that could be used to effective treat and prevent coronavirus infections and symptoms. Therefore, the instant specification does not provide adequate written description to possess the broad genus described above since the specification does not disclose a correlation between the necessary structure of the sequence and the claimed function to be maintained.
Second rejection – scope of enablement
Claim 8 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating some cardiovascular dysfunction or effects associated with a coronavirus infection, does not reasonably provide enablement for treating all cardiovascular dysfunction or effects associated with a coronavirus infection. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The Applicant’s attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
(1) The nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
1) Nature of the invention and 5) breadth of the claims: The invention is a method of treating cardiovascular dysfunction or effect associated with coronavirus infection comprising administering to a subject in need cilengitide or a variant thereof.
The claims are written such that the breadth includes any cardiovascular dysfunction or effect with any degree or amount of association to coronavirus infection, no matter how extensive or how limited.
The issue at hand is the degree of association required between the cardiovascular dysfunction/effects and coronavirus infection, and whether cardiovascular dysfunction/effects with limited or indirect association to coronavirus infection can be treated by practicing this method.
2) State of the prior art and 4) predictability or unpredictability of the art: The instant
specification teaches that cilengitide binds to αVβ3 to prevent its interaction with SARS-CoV-2 (see instant Pg 30, lines 17-20; Figure 4B; Pg 31, lines 5-7; Figure 5B and C). The instant specification also teaches examples of cardiovascular dysfunction and effects associated with a coronavirus infection can include acute inflammatory effect with hypercoagulability, platelet activation, endothelial dysfunction, deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction, disseminated intravascular coagulopathy, microvascular occlusion e.g., in the lungs, such as microthrombi in pulmonary vasculature and right ventricular dysfunction (see instant Pg 11, lines 24-28).
At the time of filing, the art recognized that certain cardiovascular dysfunction or effects were associated with coronavirus infection. For example, Nishiga teaches that cardiovascular disease is a common comorbidity in SARS and MERS (coronaviruses; see Pg 546, “The cardiovascular system and COVID-19: Underlying cardiovascular comorbidities”, first paragraph of Nishiga et al. COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives. Nat Rev Cardiol 17, 543–558 (2020).), and patients have been observed who have myocardial injury and myocarditis, arrhythmias, acute coronary syndrome, heart failure, sudden cardiac arrest, coagulation abnormalities and thrombosis (Pg 547, “Diverse cardiovascular manifestations,” first paragraph – Pg 550, “Coagulation abnormalities and thrombosis,” right column).
Nishiga teaches that while the mechanism underlying the development of COVID-19-related cardiovascular injury is not known, ACE2 expression is thought to be one of the major factors involved in the biological mechanism underlying tissue-specific infection as ACE2 is highly expressed in the heart and blood vessels (Pg 551, “ACE2 and cardiovascular manifestations,” first paragraph). However, based on the mechanism described in the instant application, cilengitide must bind to αVβ3 to effectively treat cardiovascular dysfunction and effects associated with coronavirus infection. Thus, one skilled in the art would predict that cilengitide may not be able to effectively treat all cardiovascular dysfunction effects associated with coronavirus infection.
3) The relative skill of those in the art: The relative skill of those in the art is high.
6) The amount of direction or guidance presented: At the time of filing, no direction or
guidance was presented in either the prior art or the instant specification that would enable one to administer cilengitide to treat the breadth of coronavirus infection-associated cardiovascular dysfunction or effects as claimed.
7) The presence or absence of working examples: The instant specification teaches one example in which administration of cilengitide inhibits viral attachment to endothelial αVβ3 and in turn prevented VE-cadherin reduction during infection (see instant Pg 30, “Vascular permeability and disruption of the intercellular junctions…”).
8) The quantity of experimentation necessary: As only a single working example is present in the instant specification, reasonable guidance with respect to treating coronavirus infection-associated cardiovascular dysfunction or effects through administration of cilengitide or a functional variant thereof was limited. Consequently, one skilled in the art would be burdened with undue experimentation to determine the precise parameters and conditions necessary to effectively treat all coronavirus infection-associated cardiovascular dysfunction or effects.
Therefore, in view of the Wands factors, as discussed above, Applicants fail to provide information sufficient to practice the claimed invention for the treatment of all coronavirus infection-associated cardiovascular dysfunction or effects.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
First rejection
Claim(s) 1, 4-10, and 14 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Picard et al. (WO2010/136168, listed as AU20100252280A1 on form PTO-892, published 12/2/2010).
Regarding claims 1 and 4, Picard teaches a method of treating cancer comprising administering cilengitide to a patient in need thereof (Abstract; claims 42 and 43; cilengitide is equivalent to the peptide sequence of claim 43 per Pg 46, lines 14-16). This reads on prevention of a coronavirus infection because prevention, as described above, does not require a patient to have a coronavirus infection (see Claim Interpretation section above).
Also see MPEP 2112(I): "[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).
Regarding claims 5 and 6, teaches the preferred dosage of an active agent is 0.5-2000mg/m2 (Pg 44, lines 7-17).
Regarding claim 7, as stated above, Picard teaches a method of treating cancer comprising administering cilengitide to a patient in need thereof (Abstract; claims 42 and 43), which reads on a method of preventing loss of barrier function associated with a coronavirus infection (see Claim Interpretation section above).
Regarding claim 8, as stated above, Picard teaches a method of treating cancer comprising administering cilengitide to a patient in need thereof (Abstract; claims 42 and 43), which reads on a method of preventing loss of barrier function associated with a coronavirus infection (see Claim Interpretation section above).
Regarding claim 9, Picard teaches pharmaceutical compositions of the invention comprising carriers, diluents, and reagents (Pg 42, lines 1-6).
Regarding claim 10, Picard teaches intravenous or I.V. infusion as a means to administer active agents (Pg 15, line 27- Pg 16, line 4).
Regarding claim 14, as stated above, Picard teaches a method of treating cancer comprising administering cilengitide to a patient in need thereof (Abstract; claims 42 and 43), which reads on a method of preventing loss of barrier function associated with a coronavirus infection (see Claim Interpretation section above).
Second rejection
Claim(s) 1-4, 7-12, 14, and 16 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Peyman (US 2020/0289534 A1, published 9/17/2020, cited on IDS filed 7/20/2023).
Regarding claim 1, Peyman teaches administering a biocompatible drug that comprises one or more antiviral medications together with one or more cell pathway inhibitors dissolved in a non-toxic semifluorinated alkane, the one or more cell pathway inhibitors blocking an inflammatory response of inflamed tissue without inhibiting an immune response (Abstract).
Peyman teaches the disclosed methods can treat respiratory tract inflammatory diseases, including coronaviruses ([0038-0041, 0047, 0057, 0697]). Peyman teaches that the biocompatible drug can be cilengitide ([0697]).
The instant specification acknowledges the above teachings of Peyman (see instant Pg 2, line 25 – Pg 3, line 3).
Peyman also anticipates prevention of a coronavirus infection where Peyman teaches administering cilengitide to a subject in need thereof who does not have coronavirus infection (see, for instance, treatment of other viruses in [0046]).
Also see MPEP 2112(I): "[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).
Regarding claim 2, Peyman teaches treating SARS-CoV-2, which has an RGD domain in the receptor binding domain of the spike protein ([0039-0041, 0047, 0057, 0697]; also see Claim Interpretation section above).
Regarding claim 3, as described above, Peyman teaches that the subject can have COVID-19 as caused by SARS-CoV-2 ([0038-0041, 0047, 0057, 0697]).
Regarding claim 4, as stated above, Peyman teaches administering cilengitide to treat a coronavirus infection ([0697]).
Regarding claim 7, the instant specification indicates that a primary manifestation of COVID-19 is the loss of endothelial barrier integrity (Pg 30, line 25). Thus, the method of treatment taught by Peyman reads on the method of early treatment of loss of barrier function associated with coronavirus infection.
Regarding claim 8, as stated above, Peyman teaches a method of treating a respiratory tract infection such as SARS-CoV-2, which causes COVID-19, by administering cilengitide. The instant specification indicates that COVID-19 has more adverse effects on the cardiovascular system as compared to other disease from coronaviruses (Pg 1, lines 24-25). Thus, the method of treatment taught by Peyman reads on the method of treating cardiovascular dysfunction associated with coronavirus infection.
Peyman also anticipates preventing cardiovascular dysfunction or effects associated with coronavirus infection where Peyman teaches administering cilengitide to a subject in need thereof who does not have coronavirus infection (see, for instance, treatment of other viruses in [0046]).
Regarding claim 9, Peyman teaches administering a biocompatible drug that comprises one or more antiviral medications together with one or more cell pathway inhibitors dissolved in a non-toxic semifluorinated alkane, the one or more cell pathway inhibitors blocking an inflammatory response of inflamed tissue without inhibiting an immune response (Abstract). Peyman further teaches that semifluorinated alkane compounds have been described for the transport of various medications (pharmaceutically acceptable carrier; [0624]).
Regarding claim 10, Peyman teaches the biocompatible drug can be administered by inhalation or intravenously ([0054]).
Regarding claim 11, Peyman teaches the biocompatible drug can be administered orally ([0054]).
Regarding claim 12, Peyman teaches administering a biocompatible drug that comprises one or more antiviral medications together with one or more cell pathway inhibitors dissolved in a non-toxic semifluorinated alkane, the one or more cell pathway inhibitors blocking an inflammatory response of inflamed tissue without inhibiting an immune response (Abstract). The one or more cell pathway inhibitors can include Rock inhibitors, Wnt inhibitors, glycogen synthesis kinase 3 (GSK-3) inhibitors, integrin inhibitors, IL-1 inhibitors, IL-6 inhibitors, and combinations thereof ([0051, 0058]). Protease inhibitors can also be combined with the one or more antiviral medications and one or more cell pathway inhibitors ([0059]).
Regarding claim 14, as stated above, Peyman teaches a method of treating a respiratory tract infection such as SARS-CoV-2, which causes COVID-19, by administering cilengitide ([0038-0041, 0047, 0057, 0697]). The instant specification indicates that a primary manifestation of COVID-19 is the loss of endothelial barrier integrity (Pg 30, line 25). Thus, the method of treatment taught by Peyman reads on the method of treating loss of barrier function associated with coronavirus infection.
Peyman also anticipates preventing loss of barrier function associated with coronavirus infection where Peyman teaches administering cilengitide to a subject in need thereof who does not have coronavirus infection (see, for instance, treatment of other viruses in [0046]).
Regarding claim 16, as described above, Peyman teaches that the subject can have COVID-19 as caused by SARS-CoV-2 ([0038-0041, 0047, 0057, 0697]).
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-12, 14, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Peyman (US 2020/0289534 A1, published 9/17/2020, cited on IDS filed 7/20/2023) in view of Picard et al. (WO2010/136168, listed as AU20100252280A1 on form PTO-892, published 12/2/2010).
The teachings of Peyman have been set forth above. Peyman does not teach administering cilengitide at a dosage of 10mg/m2 or less (claim 5) or 1mg/m2 or less (claim 6).
As stated above, Picard teaches a method of treating cancer comprising administering cilengitide to a patient in need thereof, which reads on a method of preventing coronavirus infection (Abstract; claims 42 and 43; cilengitide is equivalent to the peptide sequence of claim 43 per Pg 46, lines 14-16; also see Claim Interpretation section above). Picard teaches the preferred dosage of an active agent is 0.5-2000mg/m2 (Pg 44, lines 7-17).
Thus, regarding claims 5 and 6, it would be prima facie obvious to administer cilengitide at a dosage of 0.5-2000mg//m2, which reads on the claimed dosages. One skilled in the art would be motivated to do so because Picard teaches that such administrations can be used to prevent a coronavirus infection, which can serve as a useful starting point in a method of treatment of coronavirus. One would have a reasonable expectation of success given that Picard previously established dosages of cilengitide useful in the prevention of coronavirus infections and associated symptoms.
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, 8, and 14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21, 23, and 25 of copending Application No. 19/035,289 (‘289 reference application; claim set filed 5/1/2025). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘289 anticipate the instant claims.
Claim 21 of copending application No. ‘289 recites a method for treatment or prevention of sepsis in a subject in need thereof, the method comprising administering cilengitide to the subject intravenously. As noted above in the art rejections, prevention of sepsis reads on a subject without sepsis, which overlaps with the patient population instantly claimed (a subject with or without a coronavirus infection); moreover, the active step of “administering cilengitide to the subject intravenously” falls within the scope of the instant active step of “administering cilengitide to the subject”. Claims 23 and 25 similarly recite additional methods that read on preventing with the same active step.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 8, and 14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of copending Application No. 19/035,397 (‘397, reference application; claim set filed 1/23/2025). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘397 anticipate the instant claims and vice versa.
Claims 1-3 of copending application No. ‘397 each recite a method with an intended use and the active step “contacting the cell with cilengitide”. This reads on the active step in the instantly claimed methods, wherein cilengitide is administered to a subject.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sara Konopelski Snavely whose telephone number is (571)272-1841. The examiner can normally be reached Monday - Friday 9-6pm EST.
Examiner interviews are available via telephone, in-person, 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 L 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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SARA E KONOPELSKI SNAVELY/Examiner, Art Unit 1658
/Melissa L Fisher/Supervisory Patent Examiner, Art Unit 1658
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