DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
The amended claims filed 07/06/2026 are acknowledged and entered.
Claims 1, 3, 8-9 and 12-17 have been amended
Claims 2, and 4-7 are cancelled
Claim 20 is new.
Claims 1, 3, 8-17 and 20 are pending and examined on their merits.
Response to Amendment
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Objections
Nucleotide and/or Amino Acid Sequence Disclosures – Withdrawn
Applicant has corrected the informalities in the substitute specification regarding incorporation-by-reference and the objection is withdrawn.
Specification - Withdrawn
The disclosure was objected to because of the following informalities:
The specification is replete with terms which are not clear, concise and exact. Examples of some unclear, inexact or verbose terms used in the specification were provided.
The use of the term(s) which are trade name or a mark used in commerce. Applicant has corrected the informalities in the substitute specification and the objection is withdrawn.
Drawing - Withdrawn
The drawings were objected to because of the following informalities:
Color cannot be referenced in black and white pictures. Specification is amended herein to remove the mention of colors in FIG. 5. and the objection is withdrawn.
Claim Rejections - 35 USC § 112 withdrawn
The rejections for claim 1-17 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as ), second paragraph, as being indefinite is withdrawn in view of claims 1, 3, 8-9, and 12-17 amendments and claims 2 and 5-7 cancellation.
The rejection of claim 4 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends (claim 1) is withdrawn in view of Applicant’s cancellation of claim 4.
The rejection of claim 12-13 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for an isolated or purified vector or nucleic acid does not reasonably provide enablement for said non-isolated vector or nucleic acid which reads upon a transgenic animal or a transgene therein, is withdrawn in view of Applicant’s amendment of claim 12.
Claim Rejections - 35 USC § 102 withdrawn
4. The rejections of claims 1, 4-6, 9-10, 12-15 , under 35 U.S.C. 102(a)(b) as anticipated by Kemp (Cancer Gene Therapy (2019) 26:268–281), are all withdrawn in view of Applicant’s amendments to claims 1 and 15.
Rejections Maintained
Claim Rejections - 35 USC § 112 - Maintained
5. The rejections for claim 1, 3, 9-17 and 20 stand rejected under 35 U.S.C. § 112(a) as failing to comply with the written description requirement.
Applicant’s arguments have been fully considered and are not persuasive. Therefore, the rejections are maintained.
Applicant’s Arguments:
- The Specification expressly describes representative species spanning immunologically distinct categories, including:
(i) a B-cell epitope species (ReoV+RBD; ReoV-S21 P2(2), expressing a SARS- CoV-2 linear B-cell epitope);
(ii) a CD8+ T-cell epitope species (ReoV+OVA257-264); and
(iii) a tumor antigen epitope species (ReoV+p15E).
Expression of these fusion proteins was confirmed by dot blot and Western blot analysis (Specification, para. [0116]-[0139] and FIGS. 3-5). This is distinguishable from the AbbVie case, in which only structurally similar species (all derived from a single Joe-9 lineage) were described. Here, the described species represent qualitatively different categories of epitopes (e.g., viral B-cell, viral T-cell, and tumor antigens) and thus constitute a representative number of species within the recited genus.
Moreover, amended claims 1 and 15 recite a genus that is defined by a clear and specific structural platform: (i) the 1st to 250th amino acids of wild-type reovirus sigma-1 protein (SEQ ID NO: 1) fused to (ii) an antigen epitope at a position including and subsequent to the 251st amino acid. This structural definition provides the identifying characteristics of the entire genus (see MPEP § 2163(II)(3)(a)(i)(C)) and enables a person having ordinary skill in the art (PHOSITA) to insert various epitopes into the defined truncation site (nucleotides 763 to 1416 of SEQ ID NO: 2) using the reverse genetics Quick Exchange System described in the specification, without undue experimentation.
Accordingly, claims 1 and 15 comply with the written description requirement. Claims 3, 8-14, 16-17, and 20 depend upon claims 1 or 15 and comply with the written description requirement for at least the same reasons.
Examiner’s Response to Arguments
Applicant’s arguments have been carefully considered but are not found persuasive.
- (a) The Applicant argues that a total of 4 epitopes described in the specification (of ReoV+RBD (Reo-RBD), ReoV+OVA257-264, REOV+p15E and ReoV-S21P2(2)) are sufficient representative number of “an epitope of a viral or tumor antigen associated with cancer or an infectious disease”.
As discusses in the previous office action, Even when several species are disclosed, these are not necessarily representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, as here, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. Since each genus recited in the instant claims is large, it would be very challenging to describe sufficient species to cover the structures of the entire genera. However, four unrelated species is certainly not adequate just as the related species of Joe-9 derivatives above were inadequate. These species do not have any structure similarity and do not represent the thousands of species within the genus and/or subgenus.
Moreover and as argued by applicant, any epitope can be inserted using the reverse genetics Quick Exchange System (not claimed by the applicant). Therefore, if any epitope can be inserted, logically, 4 epitopes are not representative of all epitopes.
Applicant argues as set forth above. Thus, for the reasons set forth above and the reasons of record, the rejection is maintained.
6. The rejections for claim 1, 3, 8-17 and 20 stand 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 (1) ReoV+RBD (Reo-RBD), ReoV+OVA257-264, REOV+p15E and ReoV-S21P2(2) (expressing SARS-CoV-2 linear B cell epitope) fusion proteins and (2) the expression or detection of SARS-CoV-2, and SARS-CoV-2 linear B cell epitope can induce an specific immune response against the specific epitope (see below), does not reasonably provide enablement for (1) any σ1-fused to any viral or tumor epitope and does not reasonably provide enablement for (2) prevention of any cancer or any infectious disease. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Applicant’s arguments have been fully considered and are not persuasive. Therefore, the rejections are maintained.
Applicant’s Arguments:
Claims 1 and 15 are amended herein to recite a list of specific cancers and infectious diseases (see Specification, para. [0027] and [0065]). Moreover, the Specification demonstrates that the sigma-1-RBD fusion protein is specifically detected by a SARS-CoV-2 neutralizing antibody in a dot blot assay (see Example 3 and FIG. 3C), which provides direct evidence that the fusion protein adopts a conformation recognizable by neutralizing antibodies. Further, the Specification demonstrates that the epitope sequence inserted into the recombinant reovirus is stably maintained even after serial passage in cell culture (see Example 7 and FIG. 7), thus establishing the practicality and genetic stability of the platform.
Additionally, the Specification further provides detailed methodology for preparing a recombinant reovirus using a reverse genetics system (see Examples 1-2), for inserting an epitope-encoding sequence at nucleotide positions 763 to 1416 of SEQ ID NO: 2 (see Examples 4-7), and for confirming expression by Western blot, RT-qPCR, and dot blot. Therefore, a PHOSITA in the field of reovirus reverse genetics, who would be familiar with the technology, would be able to practice the recited claims 1 and 15 within the enumerated scope without undue experimentation.
Accordingly, claims 1 and 15 are enabled. Claims 3, 8-14, 16-17, and 20 depend upon claims 1 or 15 and are enabled for at least the same reasons.
Examiner’s Response to Arguments Applicant’s arguments have been carefully considered but are not found persuasive.
- (a) The amendments of claims 1 and 15 identify SEQ ID NO:1 as the amino acid sequence of an attenuated reovirus σ1 protein. However the amino acid sequence of an epitope of an antigen causing cancer or an infectious disease inserted at the amino acid position including and subsequent to the 251st from the N-terminus of the fusion protein has not been identified by SEQ ID NO in claims 1 and 15. Therefore the vaccine composition consisting of SEQ ID NO: 1 fused to an epitope to be used for preventing or treating a very broad list of cancers or a very broad list of infectious diseases and a method of preventing (claim 14) or treating these diseases in a subject, Therefore, the invention encompasses a vaccine comprising the polypeptide of claim 1 to be used for treating or preventing (claim 14 (Applicant is directed to the previous office action for a detailed discussion on lack of enablement for prevention)) disorders such as any type of cancer and any infectious disease..
As explained in the previous office action, the specification, is enabling for ReoV+RBD (Reo-RBD), ReoV+OVA257-264, REOV+p15E and ReoV-S21P2(2) (expressing SARS-CoV-2 linear B cell epitope) fusion proteins. But these fusion proteins cannot be used for the treatment or prevention of any of the listed cancer or infectious diseases caused by the listed viruses. For example, a SRAS-CoV-2 RBD is specifically detected by a SARS-CoV-2 neutralizing antibody in a dot blot assay. At most, it may detect other coronaviruses but it is not likely to detect unrelated viruses that do not have the RBD sequence. Unrelated viruses have a very different life cycle and they use different cell receptors for entry. Similarly, The OVA protein or derivatives thereof, are not cancer epitopes and are not involved in human cancer
Methods for creating fusion proteins are standard molecular techniques used for researchers in labs all over the world for decades. However, the use of these methods only generates fusion proteins and nothing else. These methods do not show that any fusion proteins that is generated by a reverse genetics system is sufficient proof of functionality. Therefore, a reverse genetic system does not allow the person skilled in the art to practice the recited claims 1 and 15 within the enumerated scope without undue experimentation since the epitopes are not identified. Additional methods are needed to show functionality in the treatment (or prevention as required by claim 14. Please see 112a rejection about prevention in the previous Office Action) of cancer and/or infectious diseases for any epitope. Functionality may only be enabled for the 4 epitopes in the specification and not for any viral or cancer antigen for any of the laundry list of diseases as claimed.
Applicant argues as set forth above. Thus, for the reasons set forth above and the reasons of record, the rejection is maintained.
Claim Rejections - 35 USC § 103 - Maintained
7. Claims 1, 3, 8-17 remain rejected and new claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over the combined teachings of Kemp (previously cited) in view of Sanchez-Trincado (previously cited), Hoeben (previously cited) and Barbieri (previously cited).
As discussed in the previous office action (102 section), Kemp teaches plasmid constructs comprising: the nucleotides 1-768 of the reovirus S1 segment, (SEQ ID NO: 1 is taught by Hoeben) including the 5′ UTR, the codons for the first 252 amino acids of σ1 protein, the P2A peptide sequence (instant claim 20) and a transgene (instant claims 1, 12-14 and 20). This reads on a recombinant DNA plasmid vector (polynucleotide and virus vector) capable of expressing a polypeptide comprising an amino acid sequence of an attenuated reovirus σ1 protein (truncated at about the 251st amino acid position); and an amino acid sequence of a transgene.
Structure of the S1 segments in the various recombinant reoviruses including P2A.
PNG
media_image1.png
478
923
media_image1.png
Greyscale
Applicant’s arguments have been fully considered and are not persuasive. Therefore, the rejections are maintained.
Applicant’s Arguments:
- (A). The cited references fail to disclose all elements
Independent claims 1 and 15 as amended are not obvious over the suggested combination of Kemp in view of Sanchez-Trincado, Hoeben, and Barbieri (even if motivation existed for such a combination, which is not admitted herein), at least because the cited references fail to teach or suggest all of the claimed features.
The cited references fail to describe at least (1) the sigma-1 protein and (2) the vaccine-antigen epitope configuration recited in claims 1 and 15.
1. The sigma-1 protein
The cited references fail to describe at least the sigma-1 protein recited in claims 1 and 15. Amended claim 1 recites a polypeptide consisting of the 1st to 250th amino acids of the wild-type sigma-1 protein represented by SEQ ID NO: 1. Kemp does not describe this protein. Rather, Kemp utilizes sigma-1 derived from the jin-3 mutant strain and retains the G196R substitution that is responsible for altered cell tropism. (Kemp, Abstract.) Kemp further utilizes the first 252 amino acids of the jin-3 sigma-1 protein, not the specific RP116-derived sequence as recited in claim 1.
Similarly, Hoeben does not describe the recited RP116-derived platform. Hoeben's attenuated reovirus contains multiple mutations in addition to the 251st-position truncation mutation. This includes mutations such as L1 16P, V127A, and I300M. Accordingly, the sigma-1 protein disclosed by Hoeben does not correspond to the wild-type RP116 sigma- 1 sequence recited in amended claim 1.
Furthermore, the apparent sequence similarity identified by the Office is based largely on the fact that certain amino acid positions in SEQ ID NO: 1 are represented by "X". (OA, p. 29-30.) The actual RP116 sequence differs from the Hoeben sequence at multiple positions. In addition, the recited protein terminates at amino acid 250 as a consequence of the engineered 763CAA--763TAA mutation, whereas the truncated constructs described in the cited references are derived from different genetic backgrounds and attenuation strategies. Accordingly, the recited references fail to describe the recited sigma-1 protein.
2. The vaccine-antigen epitope configuration
The cited references fail to describe at least the vaccine-antigen epitope configuration recited in claims 1 and 15. Amended claim 1 recites an epitope of a viral or tumor antigen associated with cancer or an infectious disease fused to the sigma-1 platform. Kemp does not describe such epitopes. The inserted molecules of Kemp include iLOV, E4orf4, and GM-CSF. (Kemp, FIG. 1.) These molecules function as fluorescent proteins, apoptotic regulators, or immune-enhancing cytokines. They are not antigen epitopes that function as vaccine antigens capable of inducing antigen-specific antibody production or T-cell activation.
In contrast, claims 1 and 15 utilize vaccine-antigen epitopes (e.g., SARS-CoV-2 RBD, OVA257-264, p15E). Neither Kemp nor Hoeben discloses any such epitope fusion construct. Barbieri fails to remedy Kemp and Hoeben's deficiencies. Barbieri describes SARS-CoV-2 RBD fused to a non-toxic tetanus toxin carrier in a protein subunit vaccine platform. (Barbieri, Abstract.) While Barbieri may describe one particular antigen sequence, Barbieri does not describe fusion of that sequence to the RP116-derived attenuated reovirus sigma-1 platform as recited in claim 1.
Examiner’s Response to Arguments Applicant’s arguments have been carefully considered but are not found persuasive.
- (A.1) The Applicant argues that all the elements are not disclosed by Applicant looks at the references individually (Kemp does not disclose SEQ ID NO: 1 or Hoeben does not describe the recited RP116-derived platform and not in combination. The combination of the prior art lists all the elements. Thus, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Applicant has not sufficiently described why there is no prima facie case for obviousness. Please see previous Office Action for more details regarding the teachings of Kemp, Sanchez-Trincado, Hoeben and Barbieri relevant to the rejection under 35 U.S.C. 103. As a summary, Kemp teaches an attenuated reovirus σ1 protein; truncated at about 252st amino acid position from the N-terminus (the exact length of the truncated σ1 protein are clearly a result effective parameter that can be routinely optimized); and a transgene, This transgene can be an amino acid sequence of an epitope of an tumor or viral antigen (epitopes taught by Sanchez-Trincado and Barbieri) and Hoeben teaches SEQ ID NO: 1) and the motivation to combine these references.
In addition, Applicant argues that actual RP116 sequence differs from the Hoeben sequence at multiple positions. However, the “actual RP116 sequence” is not what is claimed but SEQ ID NO: 1. SEQ ID NO 1: has in position 116 an L and so does Hoeben’s, and in position 127 a V and so does Hoeben’s. Therefore, the mutations recited above (L116P, V127A) are not found in the comparison between SEQ ID NO: 1 and Hoeben’s sequence, Applicant is acting as their own lexicographer by defining wild type sigma 1 protein as SEQ ID NO: 1 as it is recited in claim 1 (….. wherein the attenuated reovirus sigma-1 protein consists of the 1 to 250th amino acid sequence of a wild-type reovirus sigma-1 protein truncated at the 251st amino acid position from the N-terminus, and is represented by the amino acid sequence of SEQ ID NO: 1; …). Therefore, the sequence of the art is a wild type protein as defined by applicant. SEQ ID NO: 1 has three location noted as X and X represents any amino acid and Hoeben sequence is 100% identical to SEQ ID NO: 1 and Hoeben sequence is the wild type sigma 1 protein
- (A.2) Applicant argues that the cited references fail to describe at least the vaccine-antigen epitope configuration recited in claims 1 and 15. Amended claim 1 recites an epitope of a viral or tumor antigen associated with cancer or an infectious disease. Kemp does not describe such epitopes. The inserted molecules of Kemp include iLOV, E4orf4, and GM-CSF. the Adenovirus-derived protein E4orf4 is considered a multifunctional viral antigen is involved in the induction of tumor-cell selective non-classical apoptosis (instant claim 1 requires a viral antigen with an antitumor activity) and GM-CS is an immune-enhancing cytokines (as disclosed by the applicant above so it can be considered a vaccine antigen). GM-CSF a specialized protein (cytokine) that stimulates the bone marrow to produce white blood cells and helps activate the immune system to fight infections or target cancer cells. and it can function as vaccine antigen capable of inducing antigen-specific antibody production or T-cell activation.
That being said, and as discussed in the previous Office Action, Sanchez-Trincado teaches that identifying epitopes in antigens is of great interest for a number of practical reasons, including understanding disease etiology, immune monitoring, developing diagnosis assays, and designing epitope-based vaccines. Barbieri teaches a Covid 19 vaccine (title, entire application) based on antigenic peptides comprising the SARS-CoV-2 spike protein receptor binding domain (RBD) polypeptide or portions thereof. In other words, Barbieri recognizes the antigenic nature of the RBD polypeptide (instant claim 1), even when fused to another protein, and therefore fusion proteins comprising RBD can be used as vaccines for Covid-19. As mentioned above one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Applicant has not sufficiently described why there is no prima facie case for obviousness.
Applicant’s Arguments:
- (B). There is no motivation to combine
Where the combined references are missing claimed features, a case of obviousness requires an apparent reason, based either on the references themselves or on the general knowledge in the art, by which a skilled artisan would modify the references to include the missing subject matter. See KSR Int'l Co. v. Teleflex Inc., 127 S.Ct. 1727, 82 USPQ2d 1385 (2007) (obviousness includes determining whether there was an apparent reason to combine known elements in the fashion claimed).
There is no motivation to modify Kemp in view of the cited references. At the outset, Kemp describes a fundamentally different technology and objective than claims 1 and 15. Kemp is directed to improving the anticancer efficacy of an oncolytic virus. (Kemp, Abstract.) In contrast, claims 1 and 15 are directed to an epitope-based vaccine platform using a specifically engineered attenuated reovirus. To arrive at claims 1 and 15, a PHOSITA would have been required to:
1. abandon the jin-3 mutant strain used by Kemp;
2. select the RP116 platform instead;
3. introduce the specific RP116-based truncation represented by SEQ ID NO: 1;
4. replace immune-enhancing transgenes with vaccine-antigen epitopes; and
5. repurpose the oncolytic virus platform into a vaccine platform.
Examiner’s Response to Traversal: Applicant’s arguments have been carefully considered but are not found persuasive.
- (B) This is not persuasive because, as discussed above, there is no missing claimed features with the combination of the references.
Please see the previous Office Action for the discussion on the motivation to combine in view of the cited references. Kemp does not describe a fundamentally different technology and objective as the instant application Applicant just simply describes the compositions in different words. Most reovirus strains are oncolytic viruses by nature, and both Kemp and the instant application use truncated reovirus strains that are both oncolytic viruses. Kemp is directed to improving the anticancer efficacy of an attenuated Reovirus fused to a transgene (as discussed above and in the previous Office Action). Applicant is claiming an epitope-based vaccine platform using an attenuated reovirus with cancer or viral epitopes with the goal of treating a laundry list of cancer and viral diseases. According to applicant, a PHOSITA would be required to:
1. abandon the jin-3 mutant strain used by Kemp;
2. select the RP116 platform instead;
3. introduce the specific RP116-based truncation represented by SEQ ID NO: 1;
1, 2 and 3 - Jin-3 and RP116 are both oncolytic strains. Hoeben uses the same reovirus sequence as instant SEQ ID NO: 1 so the combined art teaches the wild type reovirus as claimed
4. replace immune-enhancing transgenes with vaccine-antigen epitopes;
The epitopes are found in immune-enhancing transgenes. Please see Sanchez-Trincado and Barbieri, for example, the SARS-CoV-2 RBD epitope
5. repurpose the oncolytic virus platform into a vaccine platform.
As explained above, there is no “repurposing”. Reovirus (Jin-3 and RP116 strains) are oncolytic viruses regardless of “platforms”
Applicant provided Table 1 as a claim comparison between instant claims and Kemp but as discussed above many times, references cannot be attacked individually where the rejections are based on combinations of references, which is the case here. The comparison items either ignore the combination of references or they are not limitations found in the instant claims. Please refer to the previous Office Action and all the discussion above.
Applicant’s Arguments:
- (C) There is no reasonable expectation of success
The vaccine field is highly unpredictable. The successful expression and presentation of an antigen epitope depends upon numerous factors, including:
maintenance of protein folding;
structural stability;
antigen accessibility;
retention of immunogenicity; and
genetic stability during viral replication.
Accordingly, each epitope-carrier combination requires independent validation. However, Kemp does not establish successful expression of vaccine-antigen epitopes. The transgenes utilized by Kemp were iLOV, E4orf4, and GM-CSF. The successful expression of those molecules does not provide a reasonable expectation that unrelated viral or tumor antigen epitopes would remain stably expressed and immunologically functional when fused to the RP116 sigma-1 platform. This is particularly true for structured antigens such as SARS-CoV-2 RBD.
Moreover, the present Specification demonstrates that the attenuated reovirus sigma-1-epitope fusion proteins:
" are stably expressed in host cells;
" are specifically recognized by a SARS-CoV-2 neutralizing antibody;
" induce antigen-specific immune responses; and
" maintain inserted epitope sequences after serial passage culture.
These findings establish that successful expression and immunogenic presentation of antigen epitopes on the RP116 sigma-1 platform were not predictable from the cited references. The stable expression, antigen recognition, and long-term genetic stability demonstrated in the Specification constitute strong objective evidence that the results of claims 1 and 15 would not have been reasonably expected from the cited references. Accordingly, there is no reasonable expectation of success to arrive at claims 1 and 15.
Examiner’s Response to Traversal: Applicant’s arguments have been carefully considered but are not found persuasive.
- (B) As discussed in the previous Office Action, Kemp teaches a platform comprising viruses with a truncated σ1 spike and a transgene capable of enhancing an immune response (needed for cancer or viral infection treatments) demonstrating the feasibility of such platform. Kemp’s constructs include the Adenovirus-derived protein E4orf4 and GM-CSF (see above). Barbieri teaches a Covid 19 vaccine based on antigenic peptides comprising the SARS-CoV-2 RBD linked to a noncatalytic, non-toxic tetanus toxin variant and vaccine compositions comprising the same and therefore demonstrating that fusion proteins comprising RBD can be used successfully as vaccines for Covid-19. As discussed above, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Additionally, Prior art is presumed to be operable/enabling MPEP 2121. The specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. In re Borkowski, 422 F.2d 904, 908, 164 USPQ 642, 645 (CCPA 1970). Furthermore, MPEP 2121, part III states: A prior art reference provides an enabling disclosure and thus anticipates a claimed invention if the reference describes the claimed invention in sufficient detail to enable a person of ordinary skill in the art to carry out the claimed invention; "proof of efficacy is not required for a prior art reference to be enabling for purposes of anticipation." Impax Labs. Inc. v. Aventis Pharm . Inc., 468 F.3d 1366, 1383, 81 USPQ2d 1001, 1013 (Fed. Cir. 2006). In view of the successes of the prior art, a reasonable expectation of success would be had and an absolute guarantee of the success is not required for obviousness finding.
Applicant is reminded that when the reference relied on expressly anticipates or makes obvious all of the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to provide facts rebutting the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980). Objective evidence which must be factually supported by an appropriate affidavit or declaration to be of probative value includes evidence of unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the applicant. The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965).
Furthermore, Applicant argues that the vaccine field is highly unpredictable. The successful expression and presentation of an antigen epitope depends upon numerous factors and accordingly, each epitope-carrier combination requires independent validation. However, Applicant has not explained the discrepancies of this reasoning when compared to the previous argument presented above for the 112a scope of enablement rejection when applicant claims that all members of the genus viral or tumor antigen are enabled.
There is no reason to expect that any of the antigens cited in the prior art or any other antigen cannot be successfully expressed, lack long term genetic stability or are incapable of immunogenic presentation and recognition. Attorney argument is not evidence unless it is an admission, in which case, an examiner may use the admission in making a rejection. See MPEP § 2129 and § 2144.03 for a discussion of admissions as prior art. The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997)
Applicant argues as set forth above. Thus, for the reasons set forth above and the reasons of record, the rejection is maintained.
Double Patenting - Maintained
8. Claims 1-6, 9-10, 13-14, and 17 stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 13, 22 and 24 of copending application No. 18/258,853 (US '853)
Claims 1-7, 9, and 12-14 stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 27-34, 36-41,43, 45, of copending application No. 18/694,516 (US '516).
Applicant’s Arguments:
This rejection is traverse on the ground that claims 1, 3, 9-10, 12-14, and 17 are patentably distinct from the reference applications. Both rejections are premised primarily on the assertion that SEQ ID NO: 1 of the co-pending applications is 100% identical to the recited SEQ ID NO: 1 in claim 1. However, this assertion is unreasonable in view of the novelty and non-obviousness arguments set forth above. In particular, the wild-type RP116 sigma-1-based platform of claim 1 and the sigma-1 sequences of the co-pending applications are structurally and functionally distinct. Accordingly, claim 1 and its dependent claims are patentably distinct from US '853 and US '516.
Examiner’s Response to Arguments
Applicant’s arguments have been carefully considered but are not found persuasive.
The §103 rejection combining the references listed above has been maintained and thus
the double patenting rejections based on those references is proper and is maintained for the
same reasons.
New Objections/Rejections Based on Amendments
Claim Objections
9. Claims 1, 3, 9, 14, 15, 17 are objected for the following reasons:
a. Claims 1 and 15: “….of an epitope of a viral or tumor antigen associated with cancer or an infectious disease….” should be written as “….of an epitope of a tumor or viral antigen associated with cancer or an infectious disease ….”.
b. Claims 1, 14, 15 and 17:“….rectal cancer, and brain tumor and…” should be written as “….rectal cancer, and brain tumor or…”
c. Claims 1, and 15: “…251st amino acid positions from the N terminus, and is represented by…” should be written as “…251st amino acid positions from the N terminus, and consisting of…” (see previous office action).
d. Claims 3, 9 and 15 lacks clarity since SEQ ID NO:1 is a truncated 250 amino acid sigma-1 protein (thus 750 base pairs) but SEQ ID NO: 2 is a sequence with 1416 nucleotides. Assuming that the nucleotides 1-750 code for the truncated (attenuated) 250 amino acid sigma-1 protein, it is unclear what the nucleotide sequence from 751 to 1146 represents.
e. Claim 9 lacks clarity because it recites polypeptides and nucleotides and it is unclear what the attenuated virus is (if the polypeptide of SEQ ID NO:1 or the nucleotide sequence of SEQ ID NO: 2). The claim has been interpreted to recite as follows: “ The polypeptide of claim 1, wherein the epitope is inserted after the position 250 from the N terminus of of SEQ ID NO: 1.
Claim Rejections - 35 USC § 112(b)
10. Claim 20 contains the trademark/trade name FLAG. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a tag and, accordingly, the identification/description is indefinite.
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 IMMA BARRERA whose telephone number is (571) 272-0674. The examiner can normally be reached Monday - Friday 9 to 5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, Applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Allen can be reached on (571) 270-3497. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/IMMA BARRERA/
Examiner, Art Unit 1671
/Michael Allen/Supervisory Patent Examiner, Art Unit 1671
Prosecution Insights