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 .
DETAILED ACTION
The amendment to the claims filed after non-final office action on May 22, 2026 is acknowledged. Claims 1, 5, 8-11, 22 were amended, claims 2, 6-7, 12-15, 20 and 24-27 were canceled and claims 1, 3-5, 8-11, 16-19, 21-23 are pending in the instant application. The restriction was deemed proper and made final previous office action.
Claims 3-4, 16-19, 21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claims 1, 5, 8-11, 22-23 are examined on the merits of this office action.
Withdrawn Rejections/Objections
The rejection of claims 1, 5, 8-15, 20, 22-23 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in view of amendment of the claims filed May 22, 2026.
The rejection of claims 1, 5, 8-15, 20 and 22-23 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, scope of enablement is withdrawn in view of amendment of the claims filed May 22, 2026.
The rejection of Claim(s) 1, 5, 8-9, 12-15, 23 under 35 U.S.C. 103 as being unpatentable over O’Keefe (US20100221242 A1, cited in Applicant’s IDS) in view of Tullis (WO2009149179, cited in Applicant’s IDS) and NIH RePORTER (1ZIABC011472-07, published on 2018, cited in Applicant’s IDS) is withdrawn in view of amendment of the claims filed May 22, 2026.
The rejection of claim(s) 1, 5, 8-15, 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over O’Keefe (US20100221242 A1, cited in Applicant’s IDS) in view of Tullis (WO2009149179, cited in Applicant’s IDS) and NIH RePORTER (1ZIABC011472-07, published on 2018, cited in Applicant’s IDS) as applied to claims Claim(s) 1, 5, 8-9, 12-15, 23 above in further view of Barton ((2014). Electronic Theses and Dissertations. Paper 80) is withdrawn in view of amendment of the claims filed May 22, 2026.
Maintained/Revised Rejection
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.
Claim(s) 1, 5, 8-9, 22-23 are rejected under 35 U.S.C. 103 as being unpatentable over O’Keefe (US20100221242 A1, cited in Applicant’s IDS) in view of Tullis (WO2009149179), NIH RePORTER (1ZIABC011472-07, published on 2018, cited in Applicant’s IDS) and WHO (Who position paper, published 2018).
O’Keefe teaches a method of treating/inhibiting a viral infection comprising administering Griffithsin (see claim 1, SEQ ID NO:3 is Griffithsin). O’Keefe teaches wherein the peptide comprising SEQ ID NO:2 which is identical to instant SEQ ID NO:2 (see paragraph 0030). O’Keefe teaches that the peptides having binding to high mannose oligosaccharide containing glycoproteins on the viral surface (see paragraph 0035, the end). O’Keefe teaches “In this respect, the invention provides an anti-viral conjugate comprising a Griffithsin polypeptide or fragment thereof bound to a virus or viral envelope glycoprotein. Thus the mechanism of action is due to the viral glycoprotein binding of the peptide. O’Keefe teaches combination therapy including the peptide in combination with anti-viral agents (see paragraph 0013).
O’Keefe does not expressly teach a rabies virus or in combination of rabies vaccine.
Tullis teaches antiviral methods for treating viral infections (see abstract). In particular, Tullis teaches administering a lectin affinity hemodialysis treatment, wherein said lectin binds the virus or fragment thereof (via glycoprotein binding) (see claim 1). Tullis teaches wherein the affinity binding material is Griffithsin amongst other possible binding materials (see paragraph 0040) and that that Griffithsin is a lectin that binds glycoproteins including high mannose glycoproteins (see paragraph 0042). Tullis teaches “The enhanced antiviral therapy methods disclosed herein can be used for the removal of any blood-borne viruses to which lectins bind. For example, viruses which can be cleared by the enhanced antiviral therapy methods disclosed herein include, but are not limited to…rhabdoviridae (rabies)…” (see paragraph 0107).
NIH RePORTER further evidences that griffithsin was being actively investigated for use against rabies, demonstrating recognition in the art griffithsin (a lectin) was a candidate antiviral for Rhabdoviridae.
It would have been obvious before the effective filing date of the claimed invention to administer griffithsin to treat or prevent a Rhabdoviridae infection because O’Keefe teaches griffithsin as a glycoprotein binding antiviral agent effective against enveloped RNA viruses, and Tullis teaches that lectin based glycoprotein binding antiviral methods are applicable to Rhabdoviriade, including rabies. Applying griffithsin to the Rhabdoviridae viruses identified in Tullis represents the predictable use of a known antiviral lectin for its established purpose, consistent with MPEP 2143(I)(A) and (B) (application and combination of known elements yielding predictable results.).
Additionally, because griffithsin was known as a broad spectrum antiviral lectin effective against multiple enveloped RNA viruses, and rabies is an enveloped RNA virus possessing glycosylated envelope glycoproteins, extending griffithsin to rabies would have been one of a finite number of predictable viral targets for evaluation. This supports an “obvious to try” rationale under MPEP 2143 (I)€. A reasonable expectation of success would have existed based on griffithsin’s known glycoprotein binding mechanism and Tullis’s teaching that lectin based therapies are applicable to Rhabdoviridae.
Regarding the limitation of administering a rabies vaccine in combination with griffithsin, the World Health Organization (WHO position paper, April 2018) teaches that rabies vaccination is a well-established and highly effective prophylactic and post exposure treatment for rabies (see pages 206-207). Once it would have been obvious to administer griffithsin to treat or prevent Rhabdoviridae infection including rabies (as taught by O’Keefe in view of Tullis and NIH RePORTER), combining griffithsin with the known rabies vaccine would have been an obvious matter of combining known therapies for the same condition/purpose to obtain predictable additive antiviral effect/benefit, consistent with MPEP 2144.06 (I). “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). But see In re Geiger, 815 F.2d 686, 2 USPQ2d 1276 (Fed. Cir. 1987) (“Based upon the prior art and the fact that each of the three components of the composition used in the claimed method is conventionally employed in the art for treating cooling water systems, the board held that it would have been prima facie obvious, within the meaning of 35 U.S.C. 103, to employ these components in combination for their known functions and to optimize the amount of each additive....Appellant argues... hindsight reconstruction or at best,... obvious to try’.... We agree with appellant.”). One of ordinary skilled in the art would have been motivated to combine the two each known to be useful for the same purpose (treating rabies), with a reasonable expectation that at least here will be an additive effect.
Furthermore, regarding claim 22, The WHO rabies position paper teaches that rabies prophylaxis and post exposure treatment must be administered prior to onset of neurological symptoms, as rabies becomes nearly uniformly fatal once symptoms develop (see page 206, left hand column). Once it would have been obvious to administer Griffithsin to treat or prevent Rabies infection (O’Keefe in view of Tullis), administering such therapy prior to onset of neurological signs in accordance with known rabies treatment timing would have been an obvious application of established clinical practice, consistent with MPEP2143(I)(A) and also 2144.05.
Regarding claim 5, O’Keefe teaches wherein the peptide is administered orally (see paragraph 0078). Regarding claims 8-9, O’Keefe teaches administering in single or multi doses (See paragraph 0107 and paragraph 0124, see also paragraph 0174, booster doses were administered). Regarding claim 23, O’Keefe teaches intended use in humans (see paragraph 0068, last 7 lines, paragraph 0076).
Response to Applicant’s Arguments
Applicant argues that O’Keefe teaches treating viral infections using griffithsin but not specifically a Rhabdoviridae virus, while Tullis and NIH RePORTER discloses the use of griffithsin to treat rabies. Applicant further argues that WHO teaches rabies vaccination as a highly effective prophylactic against rabies and that the Examiner improperly concludes that it would have been obvious to combine griffithsin with a rabies vaccine to treat or prevent rabies.
Applicants arguments have been fully considered but not found persuasive. As set forth in the rejection, O’Keefe teaches griffithsin as a broad spectrum antiviral agent, Tullis teaches application of lectin based antiviral therapy to Rhabdoviridae including rabies, NIH RePORTER evidences that griffithsin was actively being investigating for rabies treatment, and WHO teaches administration of rabies vaccine as an established prophylactic and post exposure therapy. Collectively, these references provide ample motivation to administer griffithsin together with a rabies vaccine for treatment or prevention of rabies vaccine for treatment or prevention of rabies with a reasonable expectation of success. The amendment reciting griffithsin comprising SEQ ID NO:2 and administration of a rabies vaccine has been fully considered but does not patentably distinguish the claimed subject matter because O’Keefe teaches the recited griffithsin protein and WHO expressly teaches administration of rabies vaccine.
Applicant argues that the cited references provide no indication that griffithsin would improve rabies vaccine efficacy or function as a vaccine adjuvant. Applicant’s arguments have been fully considered but not found persuasive. The rejection does not rely upon griffithsin functioning as a vaccine adjuvant. Rather, the rejection is based upon the obvious administration of two known anti rabies therapies for their known purposes. The pending claims merely require administration of griffithsin and a rabies vaccine and do not require griffithsin to enhance vaccine efficacy, function as an adjuvant, or produce any particular increase in antibody titers.
Applicant argues that because WHO already teaches rabies vaccine is highly effective, there would have been no motivation to add griffithsin. Applicant’s arguments have been fully considered but not found persuasive. The fact that an existing therapy is effective does not teach away from combining it with another known therapy directed to the same disease. Combination therapy is well established treatment strategy for infectious diseases to improve therapeutic outcomes. Furthermore, the specification itself recognizes that administration of rabies immune globulin together with rabies vaccine was an established combination therapy producing superior outcomes compared to vaccine alone, demonstrating that adjunctive therapy in combination with rabies vaccine was well known. Accordingly, one of ordinary skill in the art would have been motivated to combine griffithsin with the known rabies vaccine with a reasonable expectation of obtaining at least additive therapeutic benefit.
Applicant argues that the improved results outweigh any prima facie obviousness. Applicant argues that Examples 3-4 demonstrate unexpectedly improved survival when griffithsin is administered in combination with rabies vaccine compared to griffithsin alone or vaccine alone.
Applicant’s arguments have been fully considered but not found persuasive. The cited references establish a particularly strong prima facie case of obviousness. MPEP 716.01(d) states “Although the record may establish evidence of secondary considerations which are indicia of nonobviousness, the record may also establish such a strong case of obviousness that the objective evidence of nonobviousness is not sufficient to outweigh the evidence of obviousness. Newell Cos. v. Kenney Mfg. Co., 864 F.2d 757, 769, 9 USPQ2d 1417, 1427 (Fed. Cir. 1988), cert. denied, 493 U.S. 814 (1989); Richardson-Vicks, Inc., v. The Upjohn Co., 122 F.3d 1476, 1484, 44 USPQ2d 1181, 1187 (Fed. Cir. 1997) (showing of unexpected results and commercial success of claimed ibuprofen and pseudoephedrine combination in single tablet form, while supported by substantial evidence, held not to overcome strong prima facie case of obviousness). See In re Piasecki, 745 F.2d 1468, 223 USPQ 785 (Fed. Cir. 1984) for a detailed discussion of the proper roles of the examiner’s prima facie case and applicant’s rebuttal evidence in the final determination of obviousness.”
O’Keefe teaches griffithsin as a broad-spectrum antiviral lectin effective through binding viral envelope glycoproteins. Tullis expressly teaches that lectin-based antiviral therapies, including griffithsin, are applicable to Rhabdoviridae, including rabies. NIH RePORTER further evidences that griffithsin was actively being investigated as a therapeutic candidate against rabies prior to Applicant’s filing date. WHO teaches rabies vaccination as the established prophylactic and post-exposure treatment for rabies. Thus, the prior art teaches each component of the claimed method and provides ample motivation to administer griffithsin together with rabies vaccine for the common purpose of treating or preventing rabies, with a reasonable expectation of success.
Applicant’s experimental evidence does not persuasively establish that the reported results would have been unexpected over the teachings of the closest prior art. The experiments compare the claimed combination to griffithsin alone and vaccine alone rather than to the teachings of the cited references. Moreover, the prior art itself would have suggested that combining two known anti-rabies therapies would improve therapeutic outcome compared with either therapy alone. Accordingly, an observed improvement in survival following combination therapy would have been reasonably expected and does not, by itself, establish unexpected results sufficient to outweigh the strong prima facie case of obviousness.
Although Applicant reports improved survival and antibody titers under particular experimental conditions, Applicant has not provided statistical analysis demonstrating that the reported differences are statistically significant (see MPEP 716.02(b)). Additionally, the specification does not establish a consistent dose response relationship across the disclosed studies, and the experimental evidence is limited to particular hamster models and dosing regimens that are substantially narrower than the pending claims. Accordingly, the evidence is entitled to limited weight and does not overcome the prima facie case of obviousness established by O’Keefe in view of Tullis, NIH RePORTER and WHO.
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, 5, 8-11, 22-23 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 19/429802 (reference application) in view of Tullis (see above teachings), NIH RePORTER (see above teachings) and O’Keefe (see above teachings) and WHO (see above teachings). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims “A method of treating or preventing a Rhabdoviridae virus infection in a mammal comprising administering griffithsin, or a fragment or mutant thereof, to the mammal”. The instant application further claims orally administering (claim 5); single or multiple doses over one to five days up to 30 (claims 8-11); additional therapeutic including rabies vaccine (claims 12 and 20); rabies virus (claims 13-14).
Co-pending Application No. 19/429802 claims a method of treating a viral infection comprising administering a GRFT mutant (see claims 17, 1, 13), wherein the infection is HIV, SARS, coronavirus, HSV, HEPC, MERs or Niv. Co-pending Application No. 19/429802 teaches oral administration (Claim 19); an additional therapeutic moiety such as an antiviral (see claim 15). Co-pending Application No. 19/429802 is silent to treating/preventing a Rhabdoviridae or Rabies virus.
However, Tullis teaches antiviral methods for treating viral infections (see abstract). In particular, Tullis teaches administering a lectin affinity hemodialysis treatment, wherein said lectin binds the virus or fragment thereof (via glycoprotein binding) (see claim 1). Tullis teaches wherein the affinity binding material is Griffithsin amongst other possible binding materials (see paragraph 0040) and that that Griffithsin is a lectin that binds glycoproteins including high mannose glycoproteins (see paragraph 0042). Tullis teaches “The enhanced antiviral therapy methods disclosed herein can be used for the removal of any blood-borne viruses to which lectins bind. For example, viruses which can be cleared by the enhanced antiviral therapy methods disclosed herein include, but are not limited to…rhabdoviridae (rabies)…” (see paragraph 0107).
NIH RePORTER further evidences that griffithsin was being actively investigated for use against rabies, demonstrating recognition in the art griffithsin (a lectin) was a candidate antiviral for Rhabdoviridae.
It would have been obvious before the effective filing date of the claimed invention to administer griffithsin to treat or prevent a Rhabdoviridae infection because Co-pending Application No. 19/429802 teaches griffithsin (which is a lectin) as an antiviral agent effective against enveloped RNA viruses, and Tullis teaches that lectin based glycoprotein binding antiviral methods are applicable to Rhabdoviriade, including rabies. Applying griffithsin to the Rhabdoviridae viruses identified in Tullis represents the predictable use of a known antiviral lectin for its established purpose, consistent with MPEP 2143(I)(A) and (B) (application and combination of known elements yielding predictable results.).
Additionally, because griffithsin was known as a broad spectrum antiviral lectin effective against multiple enveloped RNA viruses, and rabies is an enveloped RNA virus possessing glycosylated envelope glycoproteins, extending griffithsin to rabies would have been one of a finite number of predictable viral targets for evaluation. This supports an “obvious to try” rationale under MPEP 2143 (I)€. A reasonable expectation of success would have existed based on griffithsin’s known glycoprotein binding mechanism and Tullis’s teaching that lectin based therapies are applicable to Rhabdoviridae.
Regarding the amounts/dosing of the GRFT polypeptide, s. O’Keefe does teach “For in vivo uses, the dose of a Griffithsin, variant, conjugate, fusion protein, or composition thereof, administered to an animal, particularly a human, in the context of the invention should be sufficient to effect a prophylactic or therapeutic response in the individual over a reasonable time frame. The dose used to achieve a desired anti-viral concentration in vivo (e.g., 0.1-1000 nM) will be determined by the potency of the particular Griffithsin, variant, fusion protein, or conjugate employed, the severity of the disease state of infected individuals, as well as, in the case of systemic administration, the body weight and age of the infected individual. The size of the dose also will be determined by the existence of any adverse side effects that may accompany the particular Griffithsin, variant, fusion protein, or conjugate or composition thereof, employed (see paragraph 0107)”. O’Keefe also teaches booster injections at days 13, 29, 51, 64, 100 and 195 (see paragraph 0174).
Determining the optimal number of doses, frequency of administration and treatment duration constitutes routine optimization of result effective variables, consistent with MPEP 2144.05.
Co-pending AN19/429802 is silent to wherein the second therapeutic is a Rabies vaccine.
However, the World Health Organization (WHO position paper, April 2018) teaches that rabies vaccination is a well-established and highly effective prophylactic and post exposure treatment for rabies (see pages 206-207). “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). But see In re Geiger, 815 F.2d 686, 2 USPQ2d 1276 (Fed. Cir. 1987) (“Based upon the prior art and the fact that each of the three components of the composition used in the claimed method is conventionally employed in the art for treating cooling water systems, the board held that it would have been prima facie obvious, within the meaning of 35 U.S.C. 103, to employ these components in combination for their known functions and to optimize the amount of each additive....Appellant argues... hindsight reconstruction or at best,... obvious to try’.... We agree with appellant.”). One of ordinary skilled in the art would have been motivated to combine the two each known to be useful for the same purpose (treating rabies), with a reasonable expectation that at least here will be an additive effect.
Regarding instant claim 22, Once it would have been obvious to administer Griffithsin to treat or prevent Rabies infection, administering such therapy prior to onset of neurological signs in accordance with known rabies treatment timing would have been an obvious application of established clinical practice, consistent with MPEP2143(I)(A) and also 2144.05.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Applicant’s Arguments
Applicant respectfully submits that the claimed use of the combination of griffithsin and rabies vaccine is not obvious for the reasons stated above. Not only would a person of ordinary skill in the art have lacked any motivation to combine these compositions given the Examiner's acknowledgement of how widely accepted it was in the art that rabies vaccine is already highly effective on its own, but also the significantly superior treatment and protection the combination provides was unexpected, outweighing any obviousness. Accordingly, Applicant respectfully requests that the Examiner reconsider and withdraw the nonstatutory obviousness- type double patenting rejections.
Applicants arguments have been fully considered but not found persuasive. For at least the reasons discussed above in response to Applicant’s arguments regarding the rejection under 35 U.S.C. 103, the Examiner maintains that the pending claims are not patentably distinct from the claims of the reference Co-pending Application. Accordingly, the nonstatutory obvious type double patenting rejection is maintained.
Claims 1, 5, 8-11, 22-23 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of US Patent NO. 10501507 B2 (reference application) in view of O’Keefe (see above teachings), Tullis (see above teachings), NIH RePORTER (see above teachings) and WHO (see above teachings). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims “A method of treating or preventing a Rhabdoviridae virus infection in a mammal comprising administering griffithsin, or a fragment or mutant thereof, to the mammal”. The instant application further claims orally administering (claim 5); single or multiple doses over one to five days up to 30 (claims 8-11); additional therapeutic including rabies vaccine (claims 12 and 20); rabies virus (claims 13-14).
US Patent NO. 10501507 claims a method of treating/preventing a viral infection comprising administering a GRFT mutant (see claims 1, 11-12), wherein the infection is HIV. US Patent No. ‘507 is silent to treating/preventing a Rhabdoviridae or Rabies virus; oral administration; the dosing parameters of the instant claims and including an anti-viral agent such as a rabies vaccine.
O’Keefe teaches a method of treating/inhibiting a viral infection comprising administering Griffithsin and mutants thereof (see claim 1, SEQ ID NO:3 is Griffithsin). O’Keefe teaches that the peptides having binding to high mannose oligosaccharide containing glycoproteins on the viral surface (see paragraph 0035, the end). O’Keefe teaches “In this respect, the invention provides an anti-viral conjugate comprising a Griffithsin polypeptide or fragment thereof bound to a virus or viral envelope glycoprotein. Thus the mechanism of action is due to the viral glycoprotein binding of the peptide. O’Keefe teaches wherein the peptide is administered orally (see paragraph 0078) and administering in single or multi doses (See paragraph 0107 and paragraph 0124, see also paragraph 0174, booster doses were administered). O’Keefe teaches combination therapy including the peptide in combination with anti-viral agents (see paragraph 0013). O’Keefe teaches intended use in humans (see paragraph 0068, last 7 lines, paragraph 0076).
Tullis teaches antiviral methods for treating viral infections (see abstract). In particular, Tullis teaches administering a lectin affinity hemodialysis treatment, wherein said lectin binds the virus or fragment thereof (via glycoprotein binding) (see claim 1). Tullis teaches wherein the affinity binding material is Griffithsin amongst other possible binding materials (see paragraph 0040) and that that Griffithsin is a lectin that binds glycoproteins including high mannose glycoproteins (see paragraph 0042). Tullis teaches “The enhanced antiviral therapy methods disclosed herein can be used for the removal of any blood-borne viruses to which lectins bind. For example, viruses which can be cleared by the enhanced antiviral therapy methods disclosed herein include, but are not limited to…rhabdoviridae (rabies)…” (see paragraph 0107).
NIH RePORTER further evidences that griffithsin was being actively investigated for use against rabies, demonstrating recognition in the art griffithsin (a lectin) was a candidate antiviral for Rhabdoviridae.
It would have been obvious before the effective filing date of the claimed invention to administer griffithsin or mutant thereof to treat or prevent a Rhabdoviridae infection because US Patent No. ‘507 teaches griffithsin mutant (which is a lectin) as an antiviral agent effective against enveloped RNA viruses (HIV), and Tullis teaches that lectin based glycoprotein binding antiviral methods are applicable to Rhabdoviriade, including rabies. Applying griffithsin to the Rhabdoviridae viruses identified in Tullis represents the predictable use of a known antiviral lectin for its established purpose, consistent with MPEP 2143(I)(A) and (B) (application and combination of known elements yielding predictable results.).
Additionally, because griffithsin was known as a broad spectrum antiviral lectin effective against multiple enveloped RNA viruses (taught by O’Keefe), and rabies is an enveloped RNA virus possessing glycosylated envelope glycoproteins, extending griffithsin to rabies would have been one of a finite number of predictable viral targets for evaluation. This supports an “obvious to try” rationale under MPEP 2143 (I)€. A reasonable expectation of success would have existed based on griffithsin’ s known glycoprotein binding mechanism (given it is a lectin) and Tullis’s teaching that lectin based therapies are applicable to Rhabdoviridae.
Regarding the amounts/dosing of the GRFT polypeptide, O’Keefe teaches “For in vivo uses, the dose of a Griffithsin, variant, conjugate, fusion protein, or composition thereof, administered to an animal, particularly a human, in the context of the invention should be sufficient to effect a prophylactic or therapeutic response in the individual over a reasonable time frame. The dose used to achieve a desired anti-viral concentration in vivo (e.g., 0.1-1000 nM) will be determined by the potency of the particular Griffithsin, variant, fusion protein, or conjugate employed, the severity of the disease state of infected individuals, as well as, in the case of systemic administration, the body weight and age of the infected individual. The size of the dose also will be determined by the existence of any adverse side effects that may accompany the particular Griffithsin, variant, fusion protein, or conjugate or composition thereof, employed (see paragraph 0107)”. O’Keefe also teaches booster injections at days 13, 29, 51, 64, 100 and 195 (see paragraph 0174).
Determining the optimal number of doses, frequency of administration and treatment duration and route of administration constitutes routine optimization of result effective variables, consistent with MPEP 2144.05.
US Patent No. ‘507 is silent to wherein a second therapeutic is used and it is a Rabies vaccine.
However, the World Health Organization (WHO position paper, April 2018) teaches that rabies vaccination is a well-established and highly effective prophylactic and post exposure treatment for rabies (see pages 206-207). “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). But see In re Geiger, 815 F.2d 686, 2 USPQ2d 1276 (Fed. Cir. 1987) (“Based upon the prior art and the fact that each of the three components of the composition used in the claimed method is conventionally employed in the art for treating cooling water systems, the board held that it would have been prima facie obvious, within the meaning of 35 U.S.C. 103, to employ these components in combination for their known functions and to optimize the amount of each additive....Appellant argues... hindsight reconstruction or at best,... obvious to try’.... We agree with appellant.”). One of ordinary skilled in the art would have been motivated to combine the two each known to be useful for the same purpose (treating rabies), with a reasonable expectation that at least here will be an additive effect.
Regarding instant claim 22, Once it would have been obvious to administer Griffithsin to treat or prevent Rabies infection, administering such therapy prior to onset of neurological signs in accordance with known rabies treatment timing would have been an obvious application of established clinical practice, consistent with MPEP2143(I)(A) and also 2144.05.
Response to Applicant’s Arguments
Applicant respectfully submits that the claimed use of the combination of griffithsin and rabies vaccine is not obvious for the reasons stated above. Not only would a person of ordinary skill in the art have lacked any motivation to combine these compositions given the Examiner's acknowledgement of how widely accepted it was in the art that rabies vaccine is already highly effective on its own, but also the significantly superior treatment and protection the combination provides was unexpected, outweighing any obviousness. Accordingly, Applicant respectfully requests that the Examiner reconsider and withdraw the nonstatutory obviousness- type double patenting rejections.
Applicants arguments have been fully considered but not found persuasive. For at least the reasons discussed above in response to Applicant’s arguments regarding the rejection under 35 U.S.C. 103, the Examiner maintains that the pending claims are not patentably distinct from the claims of the reference patent. Accordingly, the nonstatutory obvious type double patenting rejection is maintained.
Claims 1, 5, 8-11, 22-23 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 20-36 of Co-pending 17/641264 (reference application) in view of O’Keefe (see above teachings), Tullis (see above teachings), NIH RePORTER (see above teachings) and WHO (see above teachings). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims “A method of treating or preventing a Rhabdoviridae virus infection in a mammal comprising administering griffithsin, or a fragment or mutant thereof, to the mammal”. The instant application further claims orally administering (claim 5); single or multiple doses over one to five days up to 30 (claims 8-11); additional therapeutic including rabies vaccine (claims 12 and 20); rabies virus (claims 13-14).
Co-pending AN17/641264 claims a method of treating/preventing a viral infection comprising administering a GRFT mutant (see claims 35), wherein the infection is HIV OR SARS-CoV and oral administration (Claim 36). Co-pending AN17/641264 s silent to treating/preventing a Rhabdoviridae or Rabies virus; the dosing parameters of the instant claims and including an anti-viral agent such as a rabies vaccine.
O’Keefe teaches a method of treating/inhibiting a viral infection comprising administering Griffithsin and mutants thereof (see claim 1, SEQ ID NO:3 is Griffithsin). O’Keefe teaches that the peptides having binding to high mannose oligosaccharide containing glycoproteins on the viral surface (see paragraph 0035, the end). O’Keefe teaches “In this respect, the invention provides an anti-viral conjugate comprising a Griffithsin polypeptide or fragment thereof bound to a virus or viral envelope glycoprotein. Thus the mechanism of action is due to the viral glycoprotein binding of the peptide. O’Keefe teaches wherein the peptide is administered orally (see paragraph 0078) and administering in single or multi doses (See paragraph 0107 and paragraph 0124, see also paragraph 0174, booster doses were administered). O’Keefe teaches combination therapy including the peptide in combination with anti-viral agents (see paragraph 0013). O’Keefe teaches intended use in humans (see paragraph 0068, last 7 lines, paragraph 0076).
Tullis teaches antiviral methods for treating viral infections (see abstract). In particular, Tullis teaches administering a lectin affinity hemodialysis treatment, wherein said lectin binds the virus or fragment thereof (via glycoprotein binding) (see claim 1). Tullis teaches wherein the affinity binding material is Griffithsin amongst other possible binding materials (see paragraph 0040) and that that Griffithsin is a lectin that binds glycoproteins including high mannose glycoproteins (see paragraph 0042). Tullis teaches “The enhanced antiviral therapy methods disclosed herein can be used for the removal of any blood-borne viruses to which lectins bind. For example, viruses which can be cleared by the enhanced antiviral therapy methods disclosed herein include, but are not limited to…rhabdoviridae (rabies)…” (see paragraph 0107).
NIH RePORTER further evidences that griffithsin was being actively investigated for use against rabies, demonstrating recognition in the art griffithsin (a lectin) was a candidate antiviral for Rhabdoviridae.
It would have been obvious before the effective filing date of the claimed invention to administer griffithsin or mutant thereof to treat or prevent a Rhabdoviridae infection because Co-pending AN17/641264 teaches griffithsin mutant (which is a lectin) as an antiviral agent effective against enveloped RNA viruses (HIV), and Tullis teaches that lectin based glycoprotein binding antiviral methods are applicable to Rhabdoviriade, including rabies. Applying griffithsin to the Rhabdoviridae viruses identified in Tullis represents the predictable use of a known antiviral lectin for its established purpose, consistent with MPEP 2143(I)(A) and (B) (application and combination of known elements yielding predictable results.).
Additionally, because griffithsin was known as a broad spectrum antiviral lectin effective against multiple enveloped RNA viruses (taught by O’Keefe), and rabies is an enveloped RNA virus possessing glycosylated envelope glycoproteins, extending griffithsin to rabies would have been one of a finite number of predictable viral targets for evaluation. This supports an “obvious to try” rationale under MPEP 2143 (I)€. A reasonable expectation of success would have existed based on griffithsin’ s known glycoprotein binding mechanism (given it is a lectin) and Tullis’s teaching that lectin based therapies are applicable to Rhabdoviridae.
Regarding the amounts/dosing of the GRFT polypeptide, O’Keefe teaches “For in vivo uses, the dose of a Griffithsin, variant, conjugate, fusion protein, or composition thereof, administered to an animal, particularly a human, in the context of the invention should be sufficient to effect a prophylactic or therapeutic response in the individual over a reasonable time frame. The dose used to achieve a desired anti-viral concentration in vivo (e.g., 0.1-1000 nM) will be determined by the potency of the particular Griffithsin, variant, fusion protein, or conjugate employed, the severity of the disease state of infected individuals, as well as, in the case of systemic administration, the body weight and age of the infected individual. The size of the dose also will be determined by the existence of any adverse side effects that may accompany the particular Griffithsin, variant, fusion protein, or conjugate or composition thereof, employed (see paragraph 0107)”. O’Keefe also teaches booster injections at days 13, 29, 51, 64, 100 and 195 (see paragraph 0174).
Determining the optimal number of doses, frequency of administration and treatment duration and route of administration constitutes routine optimization of result effective variables, consistent with MPEP 2144.05.
Co-pending AN17/641264 is silent to wherein a second therapeutic is used and it is a Rabies vaccine.
However, the World Health Organization (WHO position paper, April 2018) teaches that rabies vaccination is a well-established and highly effective prophylactic and post exposure treatment for rabies (see pages 206-207). “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). But see In re Geiger, 815 F.2d 686, 2 USPQ2d 1276 (Fed. Cir. 1987) (“Based upon the prior art and the fact that each of the three components of the composition used in the claimed method is conventionally employed in the art for treating cooling water systems, the board held that it would have been prima facie obvious, within the meaning of 35 U.S.C. 103, to employ these components in combination for their known functions and to optimize the amount of each additive....Appellant argues... hindsight reconstruction or at best,... obvious to try’.... We agree with appellant.”). One of ordinary skilled in the art would have been motivated to combine the two each known to be useful for the same purpose (treating rabies), with a reasonable expectation that at least here will be an additive effect.
Regarding instant claim 22, Once it would have been obvious to administer Griffithsin to treat or prevent Rabies infection, administering such therapy prior to onset of neurological signs in accordance with known rabies treatment timing would have been an obvious application of established clinical practice, consistent with MPEP2143(I)(A) and also 2144.05.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Applicant’s Arguments
Applicant respectfully submits that the claimed use of the combination of griffithsin and rabies vaccine is not obvious for the reasons stated above. Not only would a person of ordinary skill in the art have lacked any motivation to combine these compositions given the Examiner's acknowledgement of how widely accepted it was in the art that rabies vaccine is already highly effective on its own, but also the significantly superior treatment and protection the combination provides was unexpected, outweighing any obviousness. Accordingly, Applicant respectfully requests that the Examiner reconsider and withdraw the nonstatutory obviousness- type double patenting rejections.
Applicants arguments have been fully considered but not found persuasive. For at least the reasons discussed above in response to Applicant’s arguments regarding the rejection under 35 U.S.C. 103, the Examiner maintains that the pending claims are not patentably distinct from the claims of the reference co-pending application. Accordingly, the nonstatutory obvious type double patenting rejection is maintained.
New 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.
Claim(s) 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over O’Keefe (US20100221242 A1, cited in Applicant’s IDS) in view of Tullis (WO2009149179), NIH RePORTER (1ZIABC011472-07, published on 2018, cited in Applicant’s IDS) and WHO (Who position paper, published 2018) as applied to claims Claim(s) 1, 5, 8-9, 22-23 above, in further view of Barton ((2014). Electronic Theses and Dissertations. Paper 80).
The teachings of O’Keefe in view of Tullis, NIH reporter and WHO described above.
O’Keefe teaches administration of griffithsin for antiviral therapy and contemplates multiple dosing regimens but does not specifically state administering every one to five days for 30 days or two to five doses over one to five days. O’Keefe does teach “For in vivo uses, the dose of a Griffithsin, variant, conjugate, fusion protein, or composition thereof, administered to an animal, particularly a human, in the context of the invention should be sufficient to effect a prophylactic or therapeutic response in the individual over a reasonable time frame. The dose used to achieve a desired anti-viral concentration in vivo (e.g., 0.1-1000 nM) will be determined by the potency of the particular Griffithsin, variant, fusion protein, or conjugate employed, the severity of the disease state of infected individuals, as well as, in the case of systemic administration, the body weight and age of the infected individual. The size of the dose also will be determined by the existence of any adverse side effects that may accompany the particular Griffithsin, variant, fusion protein, or conjugate or composition thereof, employed (see paragraph 0107)”. O’Keefe also teaches booster injections at days 13, 29, 51, 64, 100 and 195 (see paragraph 0174).
Barton teaches examples wherein GRFT is administering daily for 14 days (see page 28, bottom paragraph) for antiviral activity.
Determining the optimal number of doses, frequency of administration and treatment duration constitutes routine optimization of result effective variables, consistent with MPEP 2144.05. IN the absence of evidence demonstrating criticality or unexpected results associated with the recited dosing ranges, selecting 2-5 does or administration every 1-5 days for 30 days would have been an obvious matter of routine optimization.
Response to Applicant’s Arguments
Applicants reiterate the aforementioned arguments with respect to the instant rejection. The Office’s rebuttal of these arguments remains the same and is incorporated herein by reference
Conclusion
No claims are allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERINNE R DABKOWSKI whose telephone number is (571)272-1829. The examiner can normally be reached Monday-Friday 7:30-5:30 Est.
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/ERINNE R DABKOWSKI/Primary Examiner, Art Unit 1654
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