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 .
Response to Amendment
The Amendment filed 07/10/2026 in which claims 1, 3, 4, 5, 6, 7, and 11 were amended has been entered. Claims 2, 8, and 12 have been canceled.
Claims 1, 3 – 7, and 9 – 11 are under examination on the merits.
Claim Objections
(Previous objection, withdrawn) Claim 8 was objected to because of the following informalities: the claim reads “characterized in that a level of autoantibody”. The claim should read “wherein a level of autoantibody”. Appropriate correction is required.
Applicant has canceled claim 8.
Claim Interpretation
Claims 6 and 7 were interpreted as product-by-process claims. "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) See MPEP 2113.
Here, claims 6 and 7 are drawn to virus-like-particles (VLPs), and not a method for preparing VLPs. As such, for purposes of applying prior art, claims 6 and 7 were broadly interpreted herein to encompass any VLPs having all the recited structural limitations of the claimed VLPs.
Claim Rejections - 35 USC § 112 – Indefiniteness
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
(Previous rejection, withdrawn) Claims 3 and 4 were rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Applicant has amended claims 3 and 4.
(New rejection, as necessitated by the amendments) Claim 4 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 4 depends upon claim 2 which has been cancelled. These claims are therefore indefinite as it is unclear which limitations are incorporated into the claimed inventions. For purposes of compact prosecution and applying prior art, the Examiner has interpreted these claims as being dependent upon claim 1.
Claim Rejections - 35 USC § 112 – Dependence
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
(Previous rejection, withdrawn) Claim 8 was rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 8 is drawn to virus-like-particles (VLPs), and not a method for characterizing autoantibodies. The recitation of the intended use does not, absent evidence to the contrary, result in an additional structural limitation that further limit the claimed invention.
Applicant has canceled claim 8.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(Previous rejection, withdrawn) Claim(s) 1, 2, 4, 6, 9, and 10 were rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lee et al (KR101964751B1, hereinafter, “Lee”).
Applicant has amended claims 1, 4, and 6. Applicant has canceled claim 2.
(Previous rejection, withdrawn) Claims 1, 2, 6, and 8 – 12 were rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lee et al (Korean J Parasitol, 2017, hereinafter, “Lee 2”).
Applicant has amended claims 1, 6, and 11. Applicant has canceled claims 2, 8, and 12.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
(New rejection, as necessitated by amendments) Claim(s) 1, 6, 9 and 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al (KR101964751B1, hereinafter, “Lee”) in view of Roberts et al (US20210213124A1, hereinafter, “Roberts”) and Donahue et al (Molecular and Biochemical Parasitology, 2000, 10.1016/S0166-6851(00)00289-9 hereinafter, “Donahue”).
Lee teaches a Toxoplasmosis VLP which is comprised of M1 and rhoptry antigen 18 (ROP18) (Abstract). Lee teaches that this VLP can react with M1 antibodies (Figure 1, ¶0027). Lee also teaches that Rop18 specific T cells are produced upon VLP administration (Figure 2).
Regarding claim 1, Lee teaches a composition of VLP comprised of T. gondii derived surface antigen protein and M1 (Claim 1, ¶0014, Figure 1).
Lee does not teach a VLP comprising the AMA1 protein of T. gondii.
However, Roberts teaches oral vaccines comprising antigenic proteins (Title). Roberts teaches the vaccine is comprised of a recombinant Spirulina wherein the recombinant Spirulina comprises a chimeric protein comprising an antigenic epitope translationally fused to a viral protein or a virus-like particle (VLP)-forming protein (Claim 1, Claim 6, Figure 1b and 1c). Roberts teaches the antigenic epitope of the VLP-forming protein can be from a Toxoplasma or Plasmodium (Claim 22). Roberts teaches that the antigenic epitope can be the AMA1 protein of Plasmodium (Claim 27). Roberts also teaches that the antigen can be hemagglutinin (HA), neuraminidase (NA), and matrix (M1) proteins of an influenza virus (¶0115).
Furthermore, Donahue teaches that Toxoplasma and Plasmodium AMA-1 proteins are homologs (Abstract). Donahue teaches “[t]here is a high degree of sequence similarity between TgAMA-1 and Plasmodium AMA-1, most notably in the position of conserved cysteine residues within the protein's predicted extracellular domain.”
As discussed above, claim 6 is interpreted as a product-by-process claim. As such, the product of claim 6 is a VLP comprised of a T. gondii derived surface antigen and M1. Lee discloses a composition of VLP comprised of T. gondii derived surface antigen protein and M1 (Claim 1, ¶0014, Figure 1).
Regarding claims 9 and 10, Lee teaches using western blot to detect ROP18 and M1 to detect VLPs comprised of Rop18 and M1. A kit is a collection of components. The prior art
teaches a VLP comprised of T. gondii derived surface antigen protein and M1 and using western blot to detect the antigens, which are the only component recited in the kit. Therefore, the prior art fulfills the limitations of the kit comprising a VLP comprised of T. gondii derived surface antigen protein and M1 along with western blot reagents, by teaching the components of the kit.
Lee teaches VLP comprised of M1 and a T. gondii antigen (Claim 1, ¶0014, Figure 1). Roberts teaches a VLP comprised of M1 and the Plasmodium antigen AMA1 (Figure 1b, Claim 27, ¶0115). Donahue teaches that that Toxoplasma and Plasmodium AMA-1 proteins are homologs with a high degree of sequence similarity (Abstract).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to create a VLP comprised of Toxoplasma AMA1 and M1, as taught by Roberts and Lee, because doing so would create a Toxoplasma specific detection system using a well-established VLP core. One of ordinary skill in the art would have had a reasonable expectation of success in using the Toxoplasma AMA1 as a substitution of Plasmodium AMA1 VLP antigen given that the method is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
(Previous rejection, maintained and modified as necessitated by amendments) Claim 3 is rejected under 35 U.S.C. 103 over Lee, Roberts, and Donahue as applied to claims 1, 6, 9, and 10 above, and in further view of Von der Muelbe et al (US20050032730A1, hereinafter, Von der Muelbe).
As discussed above, claims 1, 6, 9, and 10 were rendered prima facie obvious by the teachings of Lee, Roberts, and Donahue.
The reference does not teach an M1 sequence comprising of SEQ ID NO: 1.
However, regarding claim 3, Lee teaches the M1 sequence that is 99.2% identical with SEQ ID NO: 1 (reproduced below, Sequence1 is Lee M1 Seq 1; Sequence2 is SEQ ID NO: 1).
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Additionally, Von der Muelbe teaches compositions containing stabilized mRNA that are optimized for translation to be used for medical applications (Title, ¶0011). This includes an optimized sequence for M1 (Figure 1) that is the exact sequence as SEQ ID NO:1 (reproduced below, Qy is SEQ ID NO: 1, Db is Von der Muelbe).
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Lee, Roberts, Donahue and Von der Muelbe are considered to be analogous to the claim invention because they teach mechanisms and treatments for infectious agents. Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to create a VLP comprised of AMA1 and M1, as taught by Roberts and Lee, with the exact sequence taught by Von der Muelbe because doing so would result in a VLP comprising a M1 that is optimized for translation within an individual. One of ordinary skill in the art would have had a reasonable expectation of success in using the optimized sequence given that it is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
(Previous rejection, maintained and modified as necessitated by amendments) Claim 4 is rejected under 35 U.S.C. 103 over Lee, Roberts, and Donahue as applied to claims 1, 6, 9, and 10 above, and in further view of Ward et al (US20050210535A1, hereinafter, Ward). As discussed above, claim 4 depends on the now cancelled claim 2. For purposes of compact prosecution and applying prior art, claim 4 is interpreted as depending on claim 1.
As discussed above, claims 1, 6, 9, and 10 were rendered prima facie obvious by the teachings of Lee, Roberts, and Donahue.
The reference does not teach an AMA1 sequence comprising of SEQ ID NO: 2.
However, Ward teaches Toxoplasma AMA1 and Toxoplasma AMA1 binding polypeptides such as antibodies (Abstract). Ward teaches the use of these polypeptides in the treatments and prevention of Toxoplasmosis (Abstract). Ward teaches T. gondii AMA1 sequence (Claim 13). Regarding claim 4, Ward teaches a T. gondii AMA1 sequence that has 100% sequence identity to SEQ ID NO: 2 (first 480 matching amino acids reproduced below, Qy is SEQ ID NO: 2, Db is Ward).
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Lee, Roberts, Donahue and Ward are considered to be analogous to the claim invention because they teach mechanisms and treatments for infectious agents. Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to create a VLP comprised of AMA1 and M1, as taught by Roberts and Lee, with the exact sequence taught by Ward because doing so result in a VLP comprising AMA1 that is known to be effective in treating or preventing T. gondii. One of ordinary skill in the art would have had a reasonable expectation of success in using the AMA1 sequence taught by Ward given that it is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
(Previous rejection, maintained and modified as necessitated by amendments) Claim 5 is rejected under 35 U.S.C. 103 over Lee, Roberts, and Donahue as applied to claims 1, 6, 9, and 10 above, and in further view of Quan et al (Vaccine, 2008, 10.1016/j.vaccine.2008.03.055, hereinafter, “Quan”), as evidenced by Davarinejad (Quantifications of Western Blots with ImageJ, 2015).
As discussed above, claims 1, 6, 9, and 10 were rendered prima facie obvious by the teachings of Lee, Roberts, and Donahue.
The reference does not teach a T. gondii derived surface antigen and M1 at a ratio of 3:1 in an VLP.
However, Quan teaches producing a bivalent influenza VLP vaccine comprised of hemagglutinin (HA) antigen and M1 (Abstract). Quan teaches the use of this VLP in mice to detect changes in the immune response (Abstract). Regarding claim 5, Quan teaches a near 3:1 ratio of HA protein to M1 (Figure 1A, Lane 3). To determine the ratio of HA protein to M1, examiner used ImageJ.JS, an online repository of the program ImageJ. Western blot quantification was done according to routine practice as evidenced by Davarinejad (Quantifications of Western Blots with ImageJ, Steps 3 to 4). Figure 1 of Quan was uploaded and using the rectangle function, the four regions of interest were measured with each region the exact same size. The pixel intensity measurements recorded by the examiner were HA, which was subtracted by lane background, compared to M1, which was subtracted by the lane background resulting in a 2.91:1 ratio (Shown below, Figure 1 [AltContent: textbox ([img-media_image4.png]
Figure 2)][AltContent: textbox ([img-media_image5.png]
Figure 1)]shows an example of how pixel intensity was calculated, Figure 2 shows two repeated iterations for calculations (A and B)).
Lee, Roberts, Donahue, and Quan are considered to be analogous to the claim invention because they teach mechanisms and treatments for infectious agents. Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to create a VLP comprised of AMA1 and M1, as taught by Lee and Roberts, at a ratio of 3:1, as taught by Quan, because doing so would produce more antigens on the VLP allowing for a stronger antibody binding. One of ordinary skill in the art would have had a reasonable expectation of success in using a 3:1 ratio of AMA1 to M1 in a VLP given that a 3:1 ratio for antigen to core proteins in VLP is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
(Previous rejection, maintained and modified as necessitated by amendments) Claim 7 is rejected under 35 U.S.C. 103 over Lee, Roberts, Donahue, and Quan as applied to claims 1, 5, 6, 9, and 10 above, and in further view of Xue et al (Arch Virol, 2014, 10.1007/s00705-014-2178-0, hereinafter, “Xue”).
As discussed above, claim 1, 5, 6, 9, and 10 were rendered prima facie obvious by the teachings of Lee, Roberts, Donahue, and Quan.
The references do not teach co-infecting a host cell with a recombinant baculovirus comprising a gene encoding a T. gondii derived surface antigen and a recombinant baculovirus comprising a gene encoding M1. As discussed above, claim 7 is interpreted as a product-by-process claim. As such, the product of claim 7 is a VLP comprised of a T. gondii derived surface antigen and M1.
However, Xue teaches engineering chimeric influenza VLPs comprised of GP5, HA, and M1 proteins (Abstract). This VLP is used to detect the binding of antibodies within the sera of individuals (Abstract). Regarding claim 7, Xue teaches Sf9 cells were co-infected with recombinant baculoviruses encoding NA/GP5-M1, chimeric protein, and HA, an antigen, at different rations including at ratios of 0.5, 1, 3, 5, and 6 (Section: Protein expression).
Lee, Roberts, Donahue, Quan, and Xue are considered to be analogous to the claim invention because they teach VLPs as therapeutic and diagnostic methods. Lee discloses a VLP comprised of M1 core and a T. gondii antigen (Abstract). Roberts teaches a VLP comprised of M1 and the Plasmodium antigen AMA1 (Figure 1b, Claim 27, ¶0115). Donahue teaches that that Toxoplasma and Plasmodium AMA-1 proteins are homologs with a high degree of sequence similarity (Abstract). Quan teaches the ratio of VLP antigen to core, HA to M1, of 2.92:1 (Figure 1B, Lane 3). Xue teaches the ratio of antigen and core proteins within VLPs can be modified by changing the recombinant baculovirus ratios during co-infection (Section: Protein expression).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to create a VLP comprised of AMA1 and M1, as taught by Lee and Roberts, at a ratio of 3:1, as taught by Quan, by changing the recombinant baculovirus ratios during co-infection, as taught by Xue, because doing so would produce more antigens compared to the core on the VLP allowing for a stronger antibody binding. One of ordinary skill in the art would have had a reasonable expectation of success in altering the ratio of recombinant baculoviruses encoding the antigen or core protein to alter VLP antigen to core ratio given that the method is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
(Previous rejection, maintained and modified as necessitated by amendments) Claim 11 is rejected under 35 U.S.C. 103 over Lee, Roberts, and Donahue as applied to claims 1, 6, 9, and 10 above, and in further view of Lee et al (Korean J Parasitol, 2017, 10.3347/kjp.2017.55.2.143, hereinafter, “Lee 2”).
As discussed above, claim 1, 5, 6, 9, and 10 were rendered prima facie obvious by the teachings of Lee, Roberts, Donahue, and Quan.
The references do not teach a method of detecting antibodies against T. gondii and/or influenza virus in a biological sample comprising contacting the biological sample with a composition which comprises VLP comprising T. gondii AMA1 and MA1.
Lee 2 teaches the generation of VLPs comprised of M1 and T. gondii rhoptry antigen 4 (ROP4) generated using a baculovirus expression system (Abstract). Lee 2 teaches the VLPs are spherical shaped and that the ROP4 are exhibited as spikes on the VLP surface (Abstract). Lee 2 teaches that this VLP elicits an in-vivo immune response (Figure 7).
Regarding claim 11, Lee 2 teaches coating 96 well plates with VLPs comprised of Rop4 and M1 before applying p.Berghei-infected mouse sera (Figure 7 caption). Lee 2 then teaches the characterization of IgG levels using ELISA (Figure 7 caption).
Lee, Roberts, Donahue, Quan, and Lee 2 are considered to be analogous to the claim invention because they teach mechanisms and treatments for infectious agents. Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to create a VLP comprised of AMA1 and M1, as taught by Lee and Roberts, and applying sera to a 96 well plate with VLPs comprised of AMA1 and M1 to characterize IgG levels because doing so would enable the antigen specific identification of infections. One of ordinary skill in the art would have had a reasonable expectation of success in using a VLP comprising AMA1 and M1 as a component of an ELISA given that the method is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Response to Arguments
1) Applicant states amendments made to claim 7 and the cancellation of claim 8 overcomes the claim objections
Applicant has amended claim 7 and cancelled claim 8. Examiner has withdrawn the rejection.
2) Applicant states amendments made to claims 3 and 4 overcome the USC 112b – Indefiniteness rejection
Applicant has amended claims 3 and 4. Examiner has withdrawn the rejection.
3) Applicant states cancellation of claim 8 overcomes the USC 112d – Dependence rejection
Applicant has cancelled claim 8. Examiner has withdrawn the rejection.
4) Applicant states amendments made to claims 1, 4, and 11 and cancellation of claims 2 and 12 overcome the USC 102 and USC 103 rejection
Applicant’s arguments have been fully considered but are not persuasive.
Applicant has amended claim 1 to be drawn to a VLP comprising a T. gondii AMA1 and influenza M1. Applicant has amended claim 4 to no longer be drawn towards the ROP4 and ROP18 antigens. While the previously cited art does not disclose or teach a VLP comprising a AMA1, the amended claims do not overcome the teachings of the prior art. The current rejection of record, which was necessitated by applicant’s amendment to the claims, is now rejected under, inter alia, Lee, Roberts, and Donahue.
As discussed above and previously, Lee teaches a Toxoplasmosis VLP which is comprised of M1 and ROP18 (Abstract). Roberts teaches a VLP comprised of M1 and the Plasmodium antigen AMA1 (Figure 1b, Claim 27, ¶0115). Donahue teaches that that Toxoplasma and Plasmodium AMA-1 proteins are homologs with a high degree of sequence similarity (Abstract).
Together, the prior art establishes VLPs comprised of M1 and Plasmodium AMA1 as well as VLPs comprised of M1 and Toxoplasmosis antigens. One of ordinary skill in the art would have a reasonable expectation of success in engineering a VLP to be comprised of both M1 and Toxoplasmosis AMA1 because the prior art establishes that not only can AMA1 be used with VLPs but that using different antigens elicit antigen specific responses.
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 Danyal H Alam whose telephone number is (571)272-1102. The examiner can normally be reached M - F 9am - 5pm.
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/DANYAL HASSAN ALAM/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672
