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
Response to Election/Restriction filed on February 5, 2026 is acknowledged. Claims2, 6-7, 24-27 were canceled, claims 1, 3-5, 8-15, 19-23 were amended and claims 1, 3-5, 8-23 are pending in the instant application.
Election/Restrictions
Applicant elected without traverse Griffithsin (SEQ ID NO:2) from List I, rabies from List II and rabies vaccine from list III in the reply filed February 5, 2026.
The restriction is deemed proper and is made FINAL in this 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 Claims 3-4, 16-19, 21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim.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, 8-15, 20, 22-23 are examined on the merits of this office action.
Claim Rejections - 35 USC § 112, First Paragraph
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.
Claims 1, 5, 8-15, 20, 22-23 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
Scope of the claims
Claim 1 claims “A method of treating or preventing a Rhabdoviridae virus infection in a mammal comprising administering griffithsin or a fragment/mutant thereof” (claim 1).
Therefore, to meet the written description requirement of 35 U.S.C. § 112, first paragraph, the specification must disclose a representative number of species that meet both the structural and functional limitations of the genus or the specification and/or the prior art must identify the structural elements that correlate to the claimed function in a manner that demonstrates to one of ordinary skill in the art that Applicant was in possession of the claimed genus at the time the application was filed.
The claims encompass WT GRFT (SEQ ID NO:2), fragments of GRFT of any length (paragraph 0018); mutants with sequence identity as low as 30% (see paragraph 0014, 0022); variants with conservative or non conservative substitutions (paragraphs 0015-0016); variants containing synthetic amino acids (paragraph 0019); variants containing insertions, deletions additions (see paragraph 0031); and much larger constructs (see paragraph 0018). The claims further require these fragments or mutants be capable of treating or preventing Rhabdoviridae virus infection. Thus, the claims define a broad functional genus of structurally diverse polypeptides united by the functional ability to treat or prevent infection.
Actual Reduction to Practice
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The specification provides experimental support for WT GRFT in vitro neutralization of rabies virus (Example 1); pharmacokinetics and BBB penetration of WT GRFT (Example 2); post exposure survival benefit using WT GRFT in hamsters (Example 3); combination therapy of WT GRFT with rabies vaccine (Example 4). The specification does not provide experimental data for any GRFT fragment, experimental data for any mutant sequence, experimental data for any sequence with reduced identity (i.e. 30%), experimental data for insertion/deletion variants; data for chemically modified variants. Thus, only one species within the claimed genus, the WT GRFT, has been reduced to practice.
Therefore, the instant specification has failed to meet the written description requirement by actual reduction to practice of a representative number of species alone.
Sufficient relevant identifying characteristic
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination thereof.
Only WT GRFT has been demonstrated to treat rabies. No fragment has been show to retain antiviral activity. No mutant listed in Table 1 has been show to treat rabies. The specification does not identify essential residues required for antiviral binding. The specification does not identify minimal functional domains. Although SEQ ID Nos:3-10 are listed, there is no data correlating those sequences with retained antiviral function against rabies. Further, fragments are defined as being any length (paragraph 0018) and mutants may have identity as low as 30% (see paragraph 0014), yet no structural guidance is provided identifying which regions are required for biological activity.
Physical/Chemical Properties
The specification describes amino acid substitutions (paragraph 0015-0016); conservative substitution categories; synthetic amino acids (paragraph 0019); glycosylation and chemical modifications (paragraph 0030); insertions and deletions (see paragraph 0031). However, the specification does not describe structural features responsible for glycan binding relevant to rabies neutralization; physical properties required for antiviral activity; and structurally motifs necessary for binding rabies virus glycoprotein. Merely describing general categories of substitutions and modifications does not demonstrate possession of specific structural configurations that retain antiviral efficacy.
Functional characteristics when coupled with a known or disclosed correlation between function and structure:
The specification defines mutants and fragments functionally as those that “Retain biological activity” and “retain the ability to treat or prevent Rhabdoviridae infection” (paragraph 0014, 0018). The specification does not correlate specific mutations with retained rabies efficacy or antiviral activity. The specification does not identify structural features common to functional variants and demonstrate which deletions preserve activity. Applicants do not establish that variants/mutants with 30% identity would retain lectin binding or antiviral activity. In the instant case, the specification describes the intended result but does not demonstrate possession of the full structural genus capable of achieving the intended result.
Method of Making
The specification describes general methods for producing polypeptides, including recombinant expression and chemical synthesis (See paragraph 0032). While these disclosures may enable one to make variants, the written description requirement is distinct form enablement. The ability to make numerous variants does not demonstrate that the inventors possessed the specific genus of fragments and mutants capable of treating or preventing Rhabdoviridae infection.
Conclusion
The specification demonstrates possession of wild type GRFT for treatment of rabies virus infection. However, it does not demonstrate possession of the full claimed genus of fragments and mutants defined by identity ranges as low as 30% sequence identity, any fragments of any length, variants with insertions, deletions, synthetic residues, and chemical modifications and functional variants defined solely by biological activity. Because the specification does not disclose representative species across the breadth of the claimed genus no structural features common to functional members of the genus sufficient to demonstrate possession, the claims fail to satisfy the written description requirement of 35 U.S.C. 112(a).
Claims 1, 5, 8-15, 20 and 22-23 are 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 patients with rabies lyssavirus with Griffithsin does not reasonably provide enablement for treatment or prevention of any Rhabdoviridae infections. 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.
To comply with the enablement requirements of 35 U.S.C. §112, first paragraph, a specification must adequately teach how to make and how to use a claimed invention throughout its scope, without undue experimentation. Plant Genetic Systems N.V. v. DeKalb Genetics Corp., 315 F.3d 1335, 1339, 65 USPQ2d 1452, 1455 (Fed. Cir. 2003). There are a variety of factors which may be considered in determining whether a disclosure would require undue experimentation. These factors include: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The Nature of the Invention/ The breadth of the claims
A method of treating or preventing a Rhabdoviridae virus infection in a mammal comprising administering griffithsin (GRFT), or a fragment or mutant thereof, to the mammal. The invention concerns antiviral treatment and prevention of neurotropic viral infections. Rabies infections involves peripheral replication, retrograde neuronal transport and CNS invasion. Prevention of infection (as opposed to partial post infection survival) requires blocking viral establishment prior to neuronal entry. Such biological systems are complex and unpredictable. The claims encompass entire Rhabdoviridae family, treatment and prevention, wild type GRFT, fragments/mutants and multiple routes and regimens.
The State of the Prior Art
The specification does not establish that GRFT was known in the art to treat or prevent Rhabdoviridae infections broadly. There is no evidence that antiviral lectins predictably neutralize all members of Rhabdoviridae. Shepherd teaches “The viral family Rhabdoviridae comprises over 140 different viral species, the most well-known being the Rabies lyssavirus, the principle cause of rabies. There are, however, a large number of other viruses within the Rhabdoviridae family that are less well studied but may also represent human pathogens” (see Abstract). Additionally, Shepherd teaches that “The family Rhabdoviridae constitutes a group of viruses infecting a diverse range of hosts, including vertebrates (including mammals, birds, reptiles, and fish), invertebrates, plants, fungi, and protozoans. Rhabdoviridae sits within the order Mononegavirales, with over 230 viruses currently assigned to the family.. The family has recently been divided into three large subfamilies: Alpharhabdovirinae, Betarhabdovirinae, and Gammarhabdovirinae. In addition, there are several more divergent viral genera currently unassigned to a subfamily. Viruses in Alpharhabdovirinae infect both vertebrates and invertebrates; those in Betarhabdovirinae infect plants and are transmitted by arthropod vectors. Viruses within Gammarhabdovirinae infect fish. Several pathogens of medical and veterinary importance exist within Alpharhabdovirinae, the foremost being Rabies lyssavirus (RABV). The routes of transmission of rhabdoviruses to humans are variable (see figure 1). Some rhabdoviruses, such as lyssaviruses, spread via direct mammal-to-mammal transmission, whilst others are transmitted by arthropod vectors or vertically. As well as classical pathogens such as RABV, there is growing evidence for other, less studied, rhabdoviruses causing human infection” (see introduction).
Regarding lyssavirus, Shepherd teaches that ABV infection causes acute encephalitis that is almost invariably fatal once the illness is clinically apparent. There is no effective treatment once disease is established, and the mainstay of prevention is bite avoidance, pre-exposure vaccination in high-risk groups, and post-exposure prophylaxis comprising rabies-specific immunoglobulin and vaccination (see section 3).
The Predictability or Unpredictability of the Art/ The Relative Skill of Those in the Art
Antiviral efficacy across viral families is not highly predictable. The Rhabdoviridae family includes multiple genera with distinct glycoproteins (see above section). The specification provides no data for vesicular stomatitis virus, other lyssaviruses or non-lyssavirus rhabdoviruses. As shown in the above art, there are many viruses that fall within Rhabdoviridae and the treatment/prevention of these viruses is highly unpredictable (see teachings of Shepherd above).
The specification does not demonstrate GRFT fragments or mutants retain efficacy. The prevention of infection is particularly unpredictable.
Amount of Guidance/ The Presence or Absence of Working Examples
The specification provides specific IM doses (5-10 mg/kg; 20 mg/kg) for treatment of rabies virus in a specific hamster model (see Examples 1-4) with GRFT. Thee specification does not provide guidance for prevention with GRFT alone administration (only examples with known vaccine), other Rhabdoviridae viruses, fragments and mutants across the claimed genus. There is no examples of GRFT alone pre-exposure prophylaxes or ample examples to reflect the broad and unpredictable genus.
The Quantity of Experimentation Necessary
To practice the full scope of the claims, a skilled artisan should test multiple Rhabdoviridae virus susceptibility, determine effective doses, establish prophylactic efficacy without a vaccine, evaluate fragments and mutants individually and confirm efficacy in multiple species. Such experimentation would not constitute routine optimization but would require extensive research. Applicants are enabled for post exposure treatment of rabies virus infection using IM administration of WT GRFT and combination therapy of GRFT with rabies vaccine. Because the specification does not enable the full scope of the claimed invention without undue experimentation, claims 1, 5, 8-15, 20, 22-23 are rejected under 35 U.S.C. 112(a) lack of enablement.
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, 12-15, 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).
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 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 does not expressly teach a Rhabdoviridae virus.
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 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 claims 12 and 15, O’Keefe teaches combination therapy including the peptide in combination with anti-viral agents (see paragraph 0013). Regarding claim 23, O’Keefe teaches intended use in humans (see paragraph 0068, last 7 lines, paragraph 0076).
Regarding claims 13-14, Rabies virus, expressly disclosed in Tullis as a Rhabdoviridae virus treatable by lectin based antiviral methods, is a member of the Lyssavirus genus thus meeting the limitations of instant claim 13.
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).
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.
Claim(s) 1, 5, 8-9, 12-15, 20, 22-23 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) 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 WHO (Who position paper, published 2018).
O’Keefe in view of Tullis and NIH Reporter are silent to wherein the second therapeutic is a Rabies vaccine and administering prior to onset of neurological signs.
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). 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.
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.
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, 8-15, 20, 22-23 are 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.
Claims 1, 5, 8-15, 20, 22-23 are 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 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.
Claims 1, 5, 8-15, 20, 22-23 are 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.
Conclusion
No claims are allowed.
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/ERINNE R DABKOWSKI/Examiner, Art Unit 1654