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 .
The response and amendment to the claims filed 5-11-2026 has been entered into the record.
Status of Claims
Claims 39-43, 45, 46, 49-51 and 53-58 are pending.
Election/Restrictions
Applicant's election with traverse of Species of SEQ ID NO:1 in the reply filed on 5-11-2026 is acknowledged. The traversal is on the ground(s) that Adams does not provide for the combination of two different iscoms of fraction A and C as claimed or provide for a dosing schedule with a delayed third as claimed. This is not found persuasive because the d independent claim and the combination with iscoms as claimed is prima facie obvious for reasons set forth below. SEQ ID NOS:2-9 are withdrawn from consideration.
The requirement is still deemed proper and is therefore made FINAL.
Information Disclosure Statement
The information disclosure statements filed 5-21-2024, 8-15-2024 and 3-20-2025 have been considered. Initialed copies are enclosed.
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 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.
Claim 58 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: 1) scope or breadth of the claims; 2) nature of the invention; 3) relative level of skill possessed by one of ordinary skill in the art; 4) state of, or the amount of knowledge in, the prior art; 5) level or degree of predictability, or a lack thereof, in the art; 6) amount of guidance or direction provided by the inventor; 7) presence or absence of working examples; and 8) quantity of experimentation required to make and use the claimed invention based upon the content of the supporting disclosure. When the above factors are weighed, it is the Examiner’s position that one skilled in the art could not practice the invention without undue experimentation.
While all of the factors have been considered, only those deemed necessary to establish a prima facie case are set forth below.
Scope or breadth of the claims
The instant claims are broadly drawn to a methods of stimulation an immune response against a Plasmodium parasite that provides for prevention of malaria with different efficacy with different time frames.
Knowledge of the prior art
The art teaches that the invasion of erythrocytes by Plasmodium merozoites is a complex, multistep process (See Chitnis et al , Cell, column 1, page 29; of record on PTOL-1449). Additionally, requirement for PvDBP with the Duffy antigen receptor for chemokines (DARC) is an absolute requirement by P. vivax for the invasion of human erythrocytes and the recognition site within PvDBP makes the receptor-ligand interaction an attractive target for intervention strategies to block invasion. In West Africa where almost 95% of the people have the Duffy-negative phenotype and are resistant to P. vivax. Chitnis et al (The journal of Experimental Medicine ,1994; of record) teach that Plasmodium knowlesi has alternate pathways for the invasion of rhesus erythrocytes that do not depend on the Duffy blood group antigen. The apparent redundancy in invasion pathways of P. knowlesi may be an important strategy. Invasion by alternate pathways has also been described for P. falciparum. The redundancy in invasion pathways may permit parasite survival in case of mutations in host receptors. (see page 505, columns 1-2). Clearly, the art teaches alternate invasion pathways and differences between animal erythrocyte invasion routes. As such, the efficacy of the protein immunogen in providing protection against malaria by means of inhibiting erythrocyte invasion by heterologous Plasmodium species in different animal models has not been demonstrated. The lack of reliable animal models to predict efficacy of experimental vaccines is a major obstacle in malaria vaccine development. Malarial vaccine candidates thus need to be tested in human clinical trials to evaluate efficacy (see Bhardwaj et al Protein Expr. Purif, 2017, page 56, column 1, first paragraph under Discussion, of record on PTOL-1449).
Guidance provided by inventor/working examples
The specification as filed provides no examples or prevention of malaria with any efficacy and for which time frame prevention would be provided as set forth in claim 58 in any animal model. The premise that antibodies that bind the immunized protein provide for prevention of malarial disease by the members of the genus Plasmodium by means of blocking invasion of erythrocytes by merozoites is not consistent across different animals erythrocytes and not consistent across different Plasmodium species as set forth by the art.
Level or degree of predictability
The degree of predictability is low given the differences in animals/humans, the differences in invasions of erythrocytes by different Plasmodium species as documented by the art and the lack of reliable animal models to test prevention and efficacy. In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity). See also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991).
Quantity of experimentation
The quantity of experimentation is vast, as the skilled artisan would have to develop reliable animal models to test various immunogenic compositions comprising SEQ ID NO:1 and variants thereof of the DBP as claimed in order to preform tests that correlate with protection from disease across various Plasmodium species as is claimed.
In light of the foregoing factors, the evidence as a whole suggests that the specification, in light of the level of knowledge in the art, does not enable one of ordinary skill to make or use the invention over the full scope of the instant claims without undue experimentation. Consequently, the claims are prima facie non-enabled.
Claims 51 and 58 are 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. As to claim 51, independent claim 39 from which it depends already provides for a first dose and a second does of the immunogenic composition and as such this claim does not properly further limit claim 39. As to claim 58, the claim does not provide for any added method steps, concentrations of agents or administration time periods and as such does not properly further limit the method of claim 39.. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 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.
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.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 39-43, 45, 46, 49-51, and 53-58 are rejected under 35 U.S.C. 103 as being unpatentable over Adams et al (US 2013/0045225) in view of Morein et al (US 10,729,764, August 4, 2020).
Adams et al teach methods of stimulation an immune response against a Plasmodium parasite in an animal or human subject comprising administering to the subject an immunogenic composition comprising an engineered Plasmodim vivax Duffy Binding Protein (PvDBPII) comprising a modified region corresponding to a dominant immunogenic polymorphic B-cell epitope region of a native PvDBPII wherein the modified region has reduced immunogenic dominance when compared to the corresponding regions of a native PvDBPII and wherein the elicited immune response has increased binding specificity for conserved Duffy binding epitopes of a Plasmodium DBP compared to an immune response generated by a natural PvDBPII (see page 31, claims 1-21) and wherein the immunogenic composition comprises the engineered PvDBPII and an immunoadjuvant (SEQ ID NO:2 of Adams et al is 97.4% identical as compared to SEQ ID NO:1 herein. Adams et al also teach the use of a combination of variants of the PvDBPII by administering an immunogenic composition comprising the variant Sal 1, 7.18 and 7 SEQ ID NOS:1, 6 and 7 respectively) or immunogenic fragments wherein the elicited immune response has increased binding specificity for conserved binding epitopes of a Plasmodium DBP compared to an immune response generated by a single natural PvDBPII (see claims 27-29). SEQ ID NOS:1, 6 and 7 are DBP polypeptides that have at least 80% with amino acid residues 194-521 SEQ ID NO:1. Adams et al teach that the proteins can be expressed in E.l coli (see pages 8-9 paragraphs [0111-0116]). Adams et al teach the immunization with initial immunization on day 0, prime boost on day 21 and anamnestic boost on day 224 (see column 14, paragraph [0163]) teaching three immunizations with the third immunization meeting the limitation of about 7 months for the third immunization dose. Day 21 meets the about 1 month parameter. Mice were immunized at 25ug/dose in adjuvant on the first and second doses (See page 17, Example 4). For Group 2 with the third immunization, the anamnestic boost at 244 days (see Example 15, page 20 and Example 18, page 22) when mice IgG levels had dropped by approximately 50% from their peak levels post second injection (see page 21 Table 2). Adams et al differ by using the adjuvant titer-max, however Adams et al teach that any adjuvant may be used.
Morein et al teach iscom preparations and the use thereof as immunomodulator or adjuvants in formulations to be used for immunizations including vaccines. The invention relates to the use of purified, semi purified or defined fractions of Quillaja saponaria Molina, in iscom and iscom-matrix adjuvanted vaccines. The use of the sapoinin preparations results in produces with increased tolerability and increased immunogenicity. The preparations may be used in methods to tailor the immunogenicity with increased control of inflammatory, hypersensitivity and allergic reactions. Adjuvant compositions comprise tow iscom particles where a first iscom particle comprises fraction A but not fraction C and a second isocom particle comprises fraction C and not fraction A (see claim 1). Fraction A comprises 50-70% by weight and Fraction C comprises 50-30% by weight of the sum of the weights of Fraction A and Fraction C (see claim 2). Other weight ratios are provided by claims 3-9. Both iscom matrix complex particles and iscom complex particles are contemplated (see claim 11). Morein et al teach hat the fractions are separately incorporated into different iscom complex or matrix (see column 5, line 56- column 7, line 3) and provided with immunogens and formulation components such as carriers and/or diluent, etc.
As to the claims, it would have been prima facie obvious to one having ordinary skill in the art at the time that the invention was filed to substitute the titer-max adjuvant in the method of stimulating an immune response to a Plasmodium parasite using the Plasmodium vivax Duffy Binding Proteins with the iscom adjuvant preparation of Morein et al because Adams et al teach that adjuvants can be used without limitation and Morein et al teach that the independent combination of A and C fraction iscoms provide for a tunable immune response that allows for increased tolerability and increased immunogenicity. It also would have been prima facie obvious to one having ordinary skill in the art at the time the invention was filed to optimize antigen dose, adjuvant dose and immunization schedules because, “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). determining suitable dosing strategies, optimum dosages and frequency of administration is a standard optimization of the treatment protocol. The method of administration, dosage and dosage frequency is a result effective variable. It is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989) As both dosages, routes of administration, dosage frequency and timing are known to the ordinary artisan, it would have been obvious to optimize the mode of administration as well as dosage amounts and frequency. It also would have been prima facie obvious to optimize the dosage regimen for an additive or synergistic therapeutic result because the general conditions of the dosages are disclosed in the prior art and it is not inventive to discover the optimum or workable ranges by routine experimentation and the art expects that dosages of the invention will vary depending upon such factors as the subject’s age, weight, height, sex, general medical conditions and previous medical conditions. Applicants are directed to In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Finally, the term “about” permits flexibility, particularly where there is nothing in the record to indicate the precise metes and bounds of the term. See, e.g. Amgen V. Chugai, 18 USPQ2d 1016 (Fed. Cir. 1991); see also MPEP 2173.05[R-6] A. The scope of the term may be considerable where the components of the respective compositions merely perform substantially the same function in substantially the same manner. See, e.g., Conopco v. May, 24 USPQ2d 1721, 1736 (U.S. District Court, Eastern District of Missouri 1992), where a four fold increase was permitted. Accordingly, the claimed amounts and time periods read on the amounts and periods disclosed in the references.
As to claim 50, it would have been prima facie obvious to administer the composition as combined in a pre-filled syringe to provide convenience and ease of administration for the health professional and that prefilled syringes are convenient means of providing the proper immunization dose to an animal or human.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Patricia Duffy whose telephone number is (571)272-0855. The examiner can normally be reached 8:00 am - 4 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Patricia Duffy/Primary Examiner, Art Unit 1645
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