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
Claims 1, 2, 22 are considered.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
For examination, the effective filing date is 1/20/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on was filed 7/19/2023. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claims 1,2,22 are objected to because of the following informalities:
- All three claims contain the following acronyms: HSV1, HSV2 and Fc. For improved form, spell out the acronyms in the first instance for each, e.g., herpes simplex virus 1 (HSV1).
- All three claims contain “cross reactive” which should be written “cross-reactive”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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, 2, and 22 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 claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, 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 inventor was in possession of the claimed genus. See, e.g., Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010); University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) at 1406; Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ("[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[T]he purpose of the written description requirement is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.' (internal quotation marks omitted).").
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. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The issue is whether the skilled artisan would understand inventor to have invented, and been in possession of, the invention as claimed.
The Federal Circuit has clarified the application of the written description requirement to inventions in the field of biotechnology. See University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568,43 USPQ2d l398, 1406 (Fed. Cir. 1997). The Court stated that a written description of an invention requires a precise definition, one that defines the structural features of the chemical genus that distinguishes it from other chemical structures. A definition by function does not suffice to define the genus because it is only an indication of what the genus does, rather than what it is. Further, the Court held that to adequately describe a claimed genus, an applicant must describe a representative number of species of the claimed genus, and that one of skill in the art should be able to “visualize or recognize the identity of the members of the genus.”
Instant claim 1 recites a nucleic acid encoding a HSV2 Fc receptor or an immunogenic fragment or variant thereof for use in inducing a cross-reactive immune response against HSV1 when administered to a subject.
Instant claim 2 recites a nucleic acid encoding a HSV1 Fc receptor or an immunogenic fragment or variant thereof for use in inducing a cross-reactive immune response against HSV2 when administered to a subject.
Instant claim 22 recites a method of treating a herpes virus infection or a herpes virus related disease in a subject in need thereof comprising administering an immunologically effective amount of nucleic acid encoding a HSV1 Fc receptor or immunogenic fragment or variant thereof, to the subject wherein the HSV1 Fc receptor or immunogenic fragment or variant thereof can induce a cross-reactive immune response against HSV2 when administered to a subject.
The Specification defines both immunogenic fragment or variant thereof below:
“[I]mmunogenic fragment” refers to a fragment of a reference antigen containing one or more epitopes (e.g., linear, conformational or both) capable of stimulating a host's immune system to make a humoral and/or cellular antigen-specific immunological response (i.e. an immune response which specifically recognizes a naturally occurring polypeptide, e.g., a viral or bacterial protein). An “epitope” is that portion of an antigen that determines its immunological specificity. T- and B-cell epitopes can be identified empirically (e.g. using PEPSCAN or similar methods). In a preferred embodiment, the immunogenic fragment induces an immune response, suitably a humoral or T cell response, which is similar to the immune response induced by the reference antigen [0179].
“Variant” is a peptide sequence that differs in sequence from a reference antigen sequence but retains at least one essential property of the reference antigen. Changes in the sequence of peptide variants may be limited or conservative, so that the sequences of the reference peptide and the variant are closely similar overall and, in many regions, identical. A variant and reference antigen can differ in amino acid sequence by one or more substitutions, additions or deletions in any combination. A variant of an antigen can be naturally occurring such as an allelic variant, or can be a variant that is not known to occur naturally. Non-naturally occurring variants of nucleic acids and polypeptides may be made by mutagenesis techniques or by direct synthesis. In a preferred embodiment, the essential property retained by the variant is the ability to induce an immune response, suitably a humoral or T cell response, which is similar to the immune response induced by the reference antigen [0176].
The specification fails to sufficiently describe the structural features that must be retained by members of the claimed genus as to establish a structure-function relationship with respect to immunogenic fragments or variants that can induce a cross-reactive immune response against HSV2 when administered to a subject and treat a herpes virus infection or herpes virus related disease. While some examples of fragments/variants are provided in the specification (e.g., different mutated versions of AS01/HSV-2 gE/gI protein)[0547], which is supportive of the Applicant having those fragments or variants in their possession, the specification is not all inclusive for other conceivable possibilities.
The Specification cannot reasonably be extrapolated and applied to support possession of the entire claimed genus of fragments and variants thereof because no one species, combination, or variant accounts for the variability amongst the claimed genus. As in Ariad, merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species. “A patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.” Brenner v. Manson, 383 U.S. 519, 536 (1966).
At best, the Specification contemplates the use of BLAST to identify functional homologs [0421-0425] based on sequence homology. However, this is not sufficient to describe members of the claimed genus because such methods access online databases that are continually being updated as sequencing technology improves. As a result, they are not a static source of information. Thus, one of skill in the art would readily appreciate that relying on a non-patent source that is continuously subject to change as a means to identify members of the claimed genus does not sufficiently meet the written description requirement.
Moreover, Friedberg (Brief Bioinformatics, 7:225-242 (2006)) teaches that homology-based transfer is not reliable for functional annotation even with high alignment percentages (page 227, second column). Friedberg also teaches that identification of functionally significant sub-regions is critical to functional annotation, and that often addition, deletion, or re-shuffling
of domains can lead to errors in annotation (page 227, second column; page 228, first paragraph). Furthermore, Friedberg teaches that sequence-based tools are just not sensitive enough to identify functional protein similarity as databases get larger, and diversity of sequences gets larger (page 228, first full paragraph).
Thornton et al. (Nature Struct. Biol, Struct. Genom. Suppl. Nov., 991-994 (2000), hereinafter “Thornton”) teaches that the same protein structure is often seen in apparently different homologous families with different functions. Thornton further describes examples of little correlation between specific enzyme function and overall protein structure (page 992, right column, at lines 2-10). Thus, when taken with the teachings of Friedberg and Thornton, one of skill in the art would readily appreciate that sequence homology alone cannot serve as the basis to describe members of the genus that have the recited function.
In the absence of a representative number of examples, the Specification must at least
describe the structural features that are required for the claimed function, in this case cross- reactive immune response induction against HSV1 or HSV2 when administered to a subject. However, as discussed above, the Specification fails to describe any substantive structural limitations as to establish a structure-function relationship with respect to immunogenic fragments or variants. The Specification also fails to describe which regions, domains, etc. of the variant sequences must be retained in order to have a “functional fragment” of the variant. Instead, Applicant merely offers a cursory statement that an immunogenic fragment or variant thereof will work.
Accordingly, the claims as currently written are not adequately described and one of skill in the art would readily appreciate that Applicant was not in possession of the claimed genus at the time of filing.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1 and 2 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. The judicial exception is not integrated into a practical application and claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below. See MPEP § 2106.04 for analysis parameters.
The instant claims are drawn to nucleic acid encoding either a HSV2 Fc receptor (as recited in claim 1) or a HSV1 Fc receptor (as recited in claim 2), i.e., composition of matter (Step 1: YES).
The nucleic acids, which can be interpreted as the genomic material of the DNA virus itself as well as a nucleic acid vaccine (e.g., DNA, RNA, mRNA), encoding the HSV1 or HSV2 Fc receptor would not, absent evidence to the contrary, exhibit any markedly different characteristics with respect to structure, function, or any other property that would diminish the nucleic acids from their naturally occurring counterparts. Jenks et al. evidences that herpesviruses [a DNA virus] encode FcR that can act as distractor receptors for host antiviral IgG, thus enabling viral evasion of host defenses (p.1).
Examples of these viral Fc receptors are glycoprotein E and glycoprotein I (Jenks, p. 6). For additional clarification, Friedman et al. also teaches HSV-1 and HSV-2 glycoprotein E function as immune evasion molecules by binding the Fc domain of an IgG molecule that is bound by its F(ab’)2 domain to its target [0005] which suggests that a cross reactive immune response could be induced as a natural phenomenon. Similarly, the Specification also discloses “an immunogenic fragment of an antigenic viral Fc receptor may be a fragment of a naturally occurring viral Fc receptor”[0180]. As such, the instant claims are directed to a judicial exception (JE) in the form of a natural phenomenon (Step 2A, Prong One: YES).
Instant claims 1 and 2 are drawn to a nucleic acid encoding either a HSV2 or a HSV1 Fc receptor. However, despite this recitation, the instant claims are drawn to a composition combined with an intended use, and not a method of actually using the composition. As such, the instant claims are limited to only the JE and do not recite any additional elements that integrate the JE into a practical application (Step 2A, Prong Two: NO).
As discussed above, the instant claims do not recite any additional elements beyond the JE. Moreover, as discussed in detail below, it was well-understood, routine, and conventional at the time of filing to isolate a nucleic acid as recited in claims 1 and 2. As such the instant claims do not recite any additional elements that amount to significantly more than the JE (Step 2B: NO).
Accordingly, the instant claims do not constitute patent eligible subject matter under 35 U.S.C. § 101.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 2, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Friedman et al. (Friedman) (US20200276300A1) (See PTO-892 Notice of References Cited) in view of Jenks et al. (Jenks) (See PTO-892 Notice of References Cited) and further in view of Balachandran et al. (Balachandran) (See PTO-892 Notice of References Cited).
Claim 1 recites: A nucleic acid encoding a HSV2 Fc receptor or an immunogenic fragment or variant thereof for use in inducing a cross-reactive immune response against HSV1 when administered to a subject.
Claim 2 recites: A nucleic acid encoding a HSV1 Fc receptor or an immunogenic fragment or variant thereof for use in inducing a cross-reactive immune response against HSV2 when administered to a subject.
Claim 22 recites: A method of treating a herpes virus infection or herpes virus related disease in a subject in need thereof comprising administering an immunologically effective amount of a nucleic acid encoding a HSV1 Fc receptor or immunogenic fragment or variant thereof, to the subject wherein the HSV1 Fc receptor or immunogenic fragment or variant thereof can induce a cross-reactive immune response against HSV2 when administered to a subject.
Friedman teaches a composition comprising modified mRNA encoding HSV-2 or HSV-1 gE or gI or fragments thereof [0058] and a method of inducing an anti-HSV immune response in a subject, the method comprising the step of administering to said subject an immunogenic composition comprising modified mRNAs encoding…(c) an HSV gE or fragment thereof as described herein, or a combination thereof [0217]. Friedman also teaches HSV-1 and HSV-2 glycoprotein E (gE) function as immune evasion molecules by binding the Fc domain of an IgG molecule that is bound by its F(ab′)2 domain to its target. Additionally, Friedman teaches
the subject is administered HSV-1 glycoproteins for methods of treating, inhibiting, suppressing, etc. an HSV-1 infection, HSV-2 infection, or a combination thereof [0210] suggesting a cross-reactive immune response to achieve the method.
While Fc binding is discussed, Friedman does not specifically teach Fc receptors.
Jenks, however, teaches “herpesviruses also encode their own viral FcRs (FcRs) [Fc receptors], which recognize the Fc regions of host immunoglobulins. These vFcRs mimic host FcRs, enabling herpesviruses to reduce and evade antiviral immune responses”(p.3). Jenks also teaches “HSV-1 encodes surface glycoproteins gE and gI, which can form a complex on infected cells or on the virion surface that binds to the Fc domain of host IgG... This complex acts as a vFcR [viral Fc receptor] and is associated with cell-to-cell spread of infection...The HSV gE-gI complex is required for the binding of monomeric non-immune IgG, but HSV gE alone is sufficient for binding polymeric IgG. Jenks also discusses HSV-2 glycoprotein E as a viral Fc receptor and its use in a vaccine (p. 6).
Neither Friedman or Jenks specifically address cross-reactivity.
Balachandran, though, teaches antigenic cross-reactions among herpes simplex virus types 1 and 2 in relation to both HSV-1 and HSV-2 glycoprotein E (gE) in Table 3 (p. 1133).
One of ordinary skill in the art would have been motivated to take into consideration Jenk’s explanation of the HSV glycoprotein E, its roles as a viral Fc receptor and how it allows HSV to evade the host immune response as well as Balachandran’s findings of cross-reactive immune response between HSV-1 and HSV-2 gE and combine both teachings with Friedman’s mRNA composition and method to arrive at the claimed invention (See MPEP 2143, G. Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention).
One of ordinary skill in the art would have had a reasonable expectation of success for combining the teachings to arrive at a method of treating a herpes virus infection or herpes virus related disease in a subject. There would have been a reasonable expectation of success given the underlying materials and methods are known within the herpes virus and nucleic acid vaccinology fields, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
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, 2, and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims of co-pending Application No. 18262033 in view of Friedman et al. (Friedman)(US20200276300A1).
The present claims are drawn to:
Claim 1: A nucleic acid encoding a HSV2 Fc receptor or an immunogenic fragment or variant thereof for use in inducing a cross reactive immune response against HSV1 when administered to a subject.
Claim 2: A nucleic acid encoding a HSV1 Fc receptor or an immunogenic fragment or variant thereof for use in inducing a cross reactive immune response against HSV2 when administered to a subject.
Claim 22: A method of treating a herpes virus infection or herpes virus related disease in a subject in need thereof comprising administering an immunologically effective amount of a nucleic acid encoding a HSV1 Fc receptor or immunogenic fragment or variant thereof, to the subject wherein the HSV1 Fc receptor or immunogenic fragment or variant thereof can induce a cross reactive immune response against HSV2 when administered to a subject
The claims of the co-pending Application No. 18262033 are drawn to:
Claim 1: An HSV2 Fc receptor or an immunogenic fragment or variant thereof for use in inducing a cross reactive immune response against HSV1 when administered to a subject.
Claim 2: An HSV1 Fc receptor or an immunogenic fragment or variant thereof for use in inducing a cross reactive immune response against HSV2 when administered to a subject.
Claim 20: A method of treating a herpes virus infection or herpes virus related disease in a subject in need thereof comprising administering an immunologically effective amount of a HSV1 Fc receptor or immunogenic fragment or variant thereof to the subject wherein the HSV1 Fc receptor or immunogenic fragment or variant thereof can induce a cross reactive immune response against HSV2 when administered to a subject.
Although the claims at issue are not identical, they are not patentably distinct from each other. The instant application claims are drawn to a nucleic acid encoding a HSV1 or HSV2 Fc receptor or an immunogenic fragment or variant thereof whereas the co-pending application claims are drawn to a HSV1 or HSV2 Fc receptor or an immunogenic fragment or variant thereof. The HSV1 or HSV2 Fc receptor, etc. of co-pending Application No. 18262033 would have been derived from HSV strains whose genome or parts of their genome are known (e.g., Genbank accessions) with genes for the “Fc receptor” of interest. Whether expressed naturally or via molecular cloning efforts, the HSV1 or HSV2 Fc receptor would still be the desired and the crucial immunogenic composition. While the rejection is directed at the claims, the specification in the co-pending application does state, “In a further aspect, the invention provides a nucleic acid encoding a HSV1 or HSV2 Fc receptor or immunogenic fragment or variant thereof of the invention” [0357]. Furthermore, and with respect to nucleic acid vaccines, Friedman teaches modified mRNAs, wherein each of said nucleoside modified mRNAs encodes a Herpes Simplex Virus (HSV) glycoprotein or immunogenic fragment thereof (claim 1).
Therefore, based on the claims in the co-pending Application No. 18262033, and Friedman’s teachings, the invention as a whole would have been prima facie obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Claire Cornelius whose telephone number is (571) 272-0860. The examiner can normally be reached M-F, 0930-1700.
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/C.C./Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672