DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
2. This Office Action is in response to the amendment filed 09 May 2024, wherein claims 1-10 were canceled and claims 11-30 were added.
Claims 11-30 are under consideration.
Priority
3. Receipt is acknowledged of certified copies of papers required by 35 CFR 1.55. Should Applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CRF 41.154(b) and 41.202(e). Therefore, the effective filing date for purposes of applying prior art is 03 November 2022.
Failure to provide a certified translation may result in no benefit being accorded for the non-English translation.
Information Disclosure Statement
4. The information disclosure statement (IDS) submitted on 09 May 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
5. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
6. Claims 11, 15-20, 22, 25-26, and 28-29 are objected to because of the following informalities:
Regarding claim 11, the target virus should be specified for clarity.
Regarding claims 15-17, “linking arm” should be rewritten as “linker” as that is the proper term for this limitation.
Regarding claims 16-17, 22, 26, and 29, a comma should be added before “and” in the lists recited for clarity.
Regarding claim 18, “once” should be replaced with “1” or “once to 10 times” should be rewritten as “up to 10 times” for proper grammar.
Regarding claim 19, “for” should be removed for clarity.
Regarding claim 20, if the amino acids of the “4 to 6 of His” are meant to be together in succession, a proper sequence identifier should be added for clarity. Similarly, if “4 of Gly and 1 of Ser” are meant to be together, they should also get a sequence identifier.
Regarding claim 25, the word “the” should be added between “of” and “polypeptide”.
Regarding claim 28, “a polypeptide” should be rewritten as “the polypeptide”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
7. 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.
8. Claims 11-30 are 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.
Regarding claims 11-13, it is unclear if “as depicted in” requires the sequences to be the full length or fragment thereof, and if the sequences can have additional amino acids or not. Examiner is interpreting this limitation to read as “comprising”, such that the sequences can be the full length or fragment thereof and can have additional amino acids. Examiner suggests changing this limitation to “of” for clarity.
Claims 12-30, which depend on claim 11, are similarly rejected.
The term “compatible” in claim 11 is a relative term which renders the claim indefinite. The term “compatible” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. All adjuvants should be usable with all antigens.
Claims 12-30, which depend on claim 11, are similarly rejected.
Regarding claim 14, “in parallel” is unclear because the structure is not readily envisioned. There could be multiple structural interpretations, such that the plurality of polypeptide antigens forms a dimerizing domain or a sort of branching structure. Examiner is interpreting this to be a branching structure. Examiner suggests rewording the claim to recite “ The polypeptide vaccine of claim 11, wherein the vaccine comprises a plurality of the polypeptide antigen.”.
See Ex parte Miyazaki, 89 USPQ2d 1207 (BPAI 2008) ("[R]ather than requiring that the claims are insolubly ambiguous, we hold that if a claim is amenable to two or more plausible claim constructions, the USPTO is justified in requiring the applicant to more precisely define the metes and bounds of the claimed invention by holding the claim unpatentable under 35 U.S.C. §112, second paragraph, as indefinite.").
Claim Rejections - 35 USC § 112(a) – Enablement
9. 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.
10. In making a determination as to whether an application has met the requirements forenablement under 35 U.S.C. 112 ¶ 1, the courts have put forth a series of factors. See, In reWands, 8 USPQ2d 1400, at 1404 (CAFC 1988). The factors considered include: (1) the breadth of the claims, (2) the nature of the invention, (3) the relative skill of those in the art, (4) the presence or absence of working examples, (5) the amount of direction or guidance provided, (6) the state of the prior art, (7) the level of predictability in the art, and (8) the quantity of experimentation necessary.
11. Claims 11-30 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a SARS-CoV-2 polypeptide immunogenic composition that is demonstrated to produce nonneutralizing antibodies for treatment of an infection, does not reasonably provide enablement for any coronavirus vaccine for treating an infection or producing neutralizing antibodies for prevention of an infection. 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/or use the invention commensurate in scope with these claims.
The claims recite a polypeptide vaccine with SEQ ID NO: 13 and/or 111, and methods for preventing or treating a coronavirus infection using the vaccine.
The nature of the invention is a polypeptide immunogenic composition.
The level of skill of one of ordinary skill in this art is high.
The specification shows that the antibodies produced binding titers to the S protein and RBD (Table 2, Table 3, and Figure 2). However, it does not make it clear in the working examples that the antibodies are capable of neutralization. The specification also states that the antigens are selected from the spike protein of SARS-CoV-2 (Page 9, line 32 to page 10, line 2; Table 1) and that they elicit an immune response (Tables 2 and 3). The specification does not discuss that the sequences would elicit an immune response to other coronaviruses.
Reasonable guidance with respect to preventing any viral infection relies on quantitative analysis from defined populations that have been successfully pre-screened and are predisposed to particular types of viruses. The essential element towards the validation of a preventive therapeutic is the ability to test the drug on subjects monitored in advance of clinical infection and link those results with subsequent histological confirmation of the presence or absence of disease. This irrefutable link between antecedent drug and subsequent knowledge of the prevention of the disease is the essence of a valid preventive agent. Further, a preventive administration also must assume that the therapeutic will be safe and tolerable for anyone susceptible to the disease. Therefore, Applicant may provide data showing prevention in vivo.
As stated in Cross v. Iizuka, 753 F.2d 1040, 1050, 224 USPQ 739, 747 (Fed. Cir. 1985): [B]ased upon the relevant evidence as a whole, there is a reasonable correlation between the disclosed in vitro utility and an in vivo activity, and therefore a rigorous correlation is not necessary where the disclosure of pharmacological activity is reasonable based upon the probative evidence. (Citations omitted.) Therefore, in the absence of the in vivo data above, Applicant may also provide evidence of pharmacological activity that would reasonably correlate with prevention of infection.
In the case of virus vaccines, a reasonable nexus exists between neutralizing antibody generation and prevention of infection. Thus, a showing that an antigen within the recited immunogen scope can produce such antibodies would support enablement for use of said antigen in a vaccine and/or methods of preventing infection therewith of the virus comprising said antigen.
Burton (2002, Nature Reviews Immunology, 2: 706-713) teaches neutralizing antibodies are crucial for vaccine-mediated protection against viral diseases (Abstract). Figure 1 divides antiviral activities of antibodies into two groups: activities against free virus and activities against infected cells. Actual block of infection (prevention of infection) is taught to be the role of neutralizing antibodies (Figure 1). Nonneutralizing antibodies thus cannot prevent infection, only treat an infection.
Adding to the unpredictability is the fact that not just any epitope of a target antigen/virus will lead to antibody generation, let alone that of neutralizing antibodies. Riddell (2000, Journal of Virology, 74(17): 8011-8017) at the abstract teaches patient sera reacts with some but not all B-cell epitopes on ORF7.1 protein. Thus, not just any epitope/antigen/immunogen will contribute to patient immunity against a virus. Sugiyama (2002, Journal of Virology, 76(4): 1691-1696) supports this by teaching in their abstract that even amongst known epitopes that lead to neutralizing antibodies in some species, another subject’s immune reaction will not necessarily generate antibodies against all said epitopes.
Burton (2011, PNAS, 108(27): 11181-11186) teaches three anti-HIV antibodies. Antibodies b12 and b6 bind CD4 binding sites while F240 binds gp41 (Abstract). All were tested for prevention of SHIV transmission to macaques (Abstract). While the two anti-gp120 antibodies have similar binding properties, b12 is strongly neutralizing and b6 is not (Abstract). F240 is nonneutralizing (Abstract). Compared to controls, the protection by b12 achieved statistical significance while no such protection was seen for either b6 or F240 (Abstract). Thus, the work of Burton supports the conclusion that neutralizing antibodies are required for prevention and so a functional vaccine should produce such. It also supports the idea that not just any peptide on protein may generate neutralizing antibodies that protect as evidenced by b12 and b6 performance above. Data is clearly required to calm the concerns of the prior art and make methods of viral infection prevention and vaccine products predictable.
Additionally, cross-reactivity between SARS-CoV-2 and other coronaviruses is not always predictable. Zech (2024, Viruses, 16, 177) teaches “Just like common cold coronaviruses, infection with one strain of SARS-CoV-2 does not efficiently protect against infection with another strain or newly emerging variants.“ (4. Evasion of Adaptive Immunity). Therefore, if infection with one strain of SARS-CoV-2 does not necessarily protect against other SARS-CoV-2 strains, it would be unpredictable that a subject would be protected from other coronaviruses from a SARS-CoV-2 vaccine. Similarly, Amanat (01 February 2023, J. Virol., 97(3)) teaches “In this study, we tested if immunity to the seasonal coronavirus spikes from OC43, HKU1, 229E, or NL63 would confer protection against SARS-CoV-2 challenge in a mouse model, and whether pre-existing immunity against these spikes would weaken the protection afforded by mRNA COVID-19 vaccination. We found that mice vaccinated with the seasonal coronavirus spike proteins had no increased protection compared to the negative controls.” (Abstract).
Taken together, it is clear from the prior art that a person of ordinary skill cannot predict the preventative power of any immunogen. They must be shown data that supports such a conclusion. Without demonstration of neutralizing antibody production, for example, in the target population with the specific immunogen, no practitioner in this art would see any given immunogen as a functional, predictable prophylactic agent. In addition, it is clear from the prior art that a person of ordinary skill would also be unable to predict the cross-reactivity between coronaviruses and thus without data proving otherwise, one would not be able to assume the nexus between vaccination with a SARS-CoV-2 antigen and protection against other coronaviruses.
In view of the lack of predictability of the art to which the invention pertains as evidenced by the art above, the lack of guidance and direction provided by Applicant, and the absence of working examples, undue experimentation would be required to make and use the invention to its full scope.
Claim Rejections - 35 USC § 102
12. 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
13. Claims 11-13, 26, and 28-30 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Georges (US 20220072121 A1; Published 10 March 2022, CON 12 February 2021).
For the purposes of compact and this rejection, prior art was applied to the enabled embodiments of claims 11-13 as discussed supra (i.e., a polypeptide vaccine with sequences that can be the full-length or fragment thereof, and may have additional amino acids, of SEQ ID NOs: 13 and 111).
Regarding claims 11-13, Georges teaches “ The immunogenic composition of any prior aspect, wherein the SARS-CoV-2 antigen coding sequence encodes a spike protein receptor binding domain (RBD) sequence, or immunogenic fragment thereof, and/or comprises an amino acid sequence of […] SEQ ID NO: 23 […] SEQ ID NO: 446 […] or an immunogenic fragment thereof.” (¶ [0264]) and may further include an adjuvant (¶ [0206] and [0280]). SEQ ID NO: 23 of Georges (‘Db’) has a 100% match to SEQ ID NO: 13 of the Instant Application (‘Qy’):
PNG
media_image1.png
189
632
media_image1.png
Greyscale
SEQ ID NO: 446 of Georges (‘Db’) has a 100% match to SEQ ID NO: 111 of the Instant Application (‘Qy’):
PNG
media_image2.png
201
628
media_image2.png
Greyscale
Therefore, Georges teaches a polypeptide vaccine with SEQ ID NO: 13 or SEQ ID NO: 111, and an adjuvant. A person of ordinary skill would not envision this to be an incompatible adjuvant.
Regarding claim 26, Georges further teaches that the adjuvant may be a cytokine (¶ [0235] and [0280]).
Regarding claims 28-30, Georges further teaches “In certain embodiments provided herein are immunogenic compositions, formulations thereof and methods of use for treating and/or preventing COVID-19 related diseases caused by SARS-Cov-2 viral infection, wherein the immunogenic composition comprises a replication defective adenoviral (rdAd) vector comprising a nucleic acid sequence encoding SEQ ID NO: 446” (¶ [0010]).
Claim Rejections - 35 USC § 103
14. 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.
15. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
16. Claims 11-16, 18-20, 26, and 28-30, are rejected under 35 U.S.C. 103 as being unpatentable over Georges (US 20220072121 A1; Published 10 March 2022, CON 12 February 2021) in view of Ella (CN 102112152 A; Published 29 June 2011).
For the purposes of compact and this rejection, prior art was applied to the enabled embodiments of claims 11-13 as discussed supra (i.e., a polypeptide vaccine with sequences that can be the full-length or fragment thereof, and may have additional amino acids, of SEQ ID NOs: 13 and 111).
Regarding claims 11-16, 18-19, and 20, Georges teaches claim 11: “ The immunogenic composition of any prior aspect, wherein the SARS-CoV-2 antigen coding sequence encodes a spike protein receptor binding domain (RBD) sequence, or immunogenic fragment thereof, and/or comprises an amino acid sequence of […] SEQ ID NO: 23 […] SEQ ID NO: 446 […] or an immunogenic fragment thereof.” (¶ [0264]) and may further include an adjuvant (¶ [0206] and [0280]). SEQ ID NO: 23 of Georges (‘Db’) has a 100% match to SEQ ID NO: 13 of the Instant Application (‘Qy’):
PNG
media_image1.png
189
632
media_image1.png
Greyscale
SEQ ID NO: 446 of Georges (‘Db’) has a 100% match to SEQ ID NO: 111 of the Instant Application (‘Qy’):
PNG
media_image2.png
201
628
media_image2.png
Greyscale
Therefore, Georges teaches a polypeptide vaccine with SEQ ID NO: 13 or SEQ ID NO: 111, and an adjuvant. A person of ordinary skill would not envision this to be an incompatible adjuvant.
Georges further teaches “In some embodiments, a single genetic construct may comprise multiple RBD variant units arranged co-linearly within a single expression cassette. […] Each RBD variant unit can be spaced from other RBD variant in the co-linear arrangement by a flexible spacer sequence comprising, for instance, glycine and serine amino acid residues. In preferred embodiments, the spacer peptide can comprise the amino acid sequence (GGGGS)n” (¶ [0198]). Georges does not teach adding multiple copies of the same antigens.
However, Ella teaches in the context of an HPV vaccine: “An object of the present invention is to enhance immunogenicity by using chimeric fusion with viral and bacterial proteins to provide multiple copies of epitopes, thereby increasing the immunogenicity of candidate vaccines.” (Page 4, ¶ 3). Therefore, it would have been obvious to one of ordinary skill before the filing date to use the one or both peptides of Georges multiple times to increase the immunogenicity of the vaccine, as discussed by Ella. A rationale to support a conclusion that a claim would have been obvious is that there is some teaching, suggestion, or motivation in the prior art or in the knowledge generally available to one of ordinary skill in the art to modify the reference or combine reference teachings, and the modification or combination would have a reasonable expectation of success. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, G. and 2143.02).
It would further be obvious to use the GGGGS spacer of Georges to connect the antigen copies. This spacer would also read on the linker of claim 16, wherein the additional serine is simply part of the antigen. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.). A rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, A. and 2143.02).
Furthermore, it would be obvious to optimize the number of epitope repetitions as the number of epitope repetitions would increase the immunogenicity, as evidenced by Ella. Therefore, one of ordinary skill would envision having four (or more) epitopes repeats in succession, as encompassed in claims 18-19. It has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980). Since Applicant has not disclosed that the specific limitations recited in instant claims are for any particular purpose or solve any stated problem, and the prior art teaches that parameter magnitudes that are encompassed by instant claims, often vary according to the sample being analyzed and various matrices, solutions and parameters appear to work equally as well, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the art.
17. Claims 11-20, 26, and 28-30 are rejected under 35 U.S.C. 103 as being unpatentable over Georges (supra) and Ella (supra) as applied to claims 11-16, 18-20, 26, and 28-30 above, and further in view of Joshi (06 September 2013, Indian J. Virol., 24(3): 312-320).
Regarding claims 14 and 17-19, Georges and Ella teach the limitations of claim 11, as discussed supra. All discussions thereon incorporated here. Neither Georges nor teach arranging the multiple epitopes in a branched arrangement.
However, Joshi teaches “Peptide dendrimers are branched architecture with higher molecular organization of peptides having stable structural configurations. They are commonly used for drug delivery, vaccine development and disease diagnosis and classified according to type of amino acid used, their chain arrangement and finally their three dimensional structures. Commonly used peptide dendrimers developed by Tam uses lysine core with 2–16 copies of similar or different peptide branches.” (Chemistry of dendrimeric designs, ¶ 1). Figure 1 shows an example of a structure with four peptides:
PNG
media_image3.png
182
322
media_image3.png
Greyscale
Furthermore, Joshi teaches “Antiviral peptides are mostly used in two forms; linear/cyclic forms and most favored multimeric form. Linear and/or cyclic forms of peptide have been used in antiviral studies against NDV [49] and Rabies [51]. However, presence of multiple binding sites for a single viral particle practically needs a large number of neutralizing peptides and may limit their applications. This shortfall of antiviral peptides strategy can be bridged by devising multimeric designs. Hall et al. [21] reported improved antiviral efficiency of anti-hantavirus peptides when used in multimeric forms” (Peptide of as antivirals, ¶ 1).
Therefore, it would have been obvious to one of ordinary skill before the filing date to take the antigens taught by Georges and further incorporate four copies into the dendrimeric design taught by Joshi, both for a better immunogenic response due to the multiple copies as discussed by Ella and the efficiency discussed by Joshi. A rationale to support a conclusion that a claim would have been obvious is that there is some teaching, suggestion, or motivation in the prior art or in the knowledge generally available to one of ordinary skill in the art to modify the reference or combine reference teachings, and the modification or combination would have a reasonable expectation of success. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, G. and 2143.02).
18. Claims 21-25 are rejected under 35 U.S.C. 103 as being unpatentable over Georges (supra), Ella (supra), and Joshi (supra) as applied to claims 11-20, 26, and 28-30 above, and further in view of Sigma-Aldrich (2016, Hemocyanin) and Kagan (30 December 2004, Cancer Immunol. Immunother., 54: 424-430).
Regarding claims 21-25, Georges and Ella make claims 11 and 14 obvious, as discussed supra. All discussions thereon incorporated here. Georges further teaches adding a carrier “the composition comprising at least one pharmaceutically acceptable diluent or carrier” (¶ [0014]). None of the references teach a carrier protein or keyhole limpet hemocyanin (KLH).
However, Sigma-Aldrich teaches “KLH is often used as a carrier protein due to its highly immunogenic properties and the large number of lysine residues available for modification.” (Product Description, ¶ 2). Kagan teaches “The epitope ratio (number of antigen molecules per KLH molecule) was determined… Tn(c) to KLH molecular epitope ratios were… 201:1… 648:1…” (Page 426, ¶ 1) and that the epitopes were covalently conjugated to KLH (Page 425, Conjugation, ¶ 1).
Therefore, it would have been obvious to one of ordinary skill before the filing date to take the composition of Georges and conjugate the epitopes KLH as the carrier. As discussed by Ella, multiple copies of the epitope will increase the immunogenicity of the vaccine. Adding KLH would further increase the vaccine’s immunogenic properties, as discussed by Sigma-Aldrich. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.). A rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, A. and 2143.02).
Furthermore, Kagan makes it obvious to conjugate a large number of epitopes to KLH. The epitope ratio will determine the amount of immunogen used in the vaccine overall and thus is a result-effective variable. Therefore, it would have been equally obvious to one of ordinary skill to use a lower number of epitopes. It has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980). Since Applicant has not disclosed that the specific limitations recited in instant claims are for any particular purpose or solve any stated problem, and the prior art teaches that parameter magnitudes that are encompassed by instant claims, often vary according to the sample being analyzed and various matrices, solutions and parameters appear to work equally as well, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the art.
19. Claim 27 is rejected under 35 U.S.C. 103 as being unpatentable over Georges (supra), Ella (supra), Joshi (supra), Sigma-Aldrich (supra), and Kagan (supra) as applied to claims 21-25 above, and further in view of ThermoScientific (2011, Imject Freund’s Adjuvants).
Regarding claims 27, Georges teaches the limitations of claim 11, as discussed supra. All discussions thereon incorporated here. While Georges discusses adding cytokine adjuvants to their composition, they do not specifically teach a complete Fruend’s adjuvant.
However, ThermoScientific teaches “Freund's adjuvants produce a stronger, longer lasting immunogenic response compared to other adjuvants. […] Thermo Scientific Imject Freund's Complete Adjuvant is the form that contains killed cells of Mycobacterium butyricum to enhance the immune response.” (Introduction, ¶ 2). Therefore, it would have been obvious to one of ordinary skill before the time of filing to take the composition of Georges and replace the cytokine adjuvant with the complete Freund’s adjuvant in order to produce a stronger and longer lasting immunogenic response, as taught by ThermoScientific. The simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, B.). A rationale to support a conclusion that a claim would have been obvious is that there is some teaching, suggestion, or motivation in the prior art or in the knowledge generally available to one of ordinary skill in the art to modify the reference or combine reference teachings, and the modification or combination would have a reasonable expectation of success. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, G. and 2143.02).
Furthermore, both Georges and ThermoScientific teach adjuvants in the context of vaccines, so it would further be obvious to combine the composition of Georges with the additional adjuvant of Thermoscientific. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.). A rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, A. and 2143.02). “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted)
Conclusion
20. No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTINA E LY whose telephone number is (571)272-5169. The examiner can normally be reached Monday - Thursday, 8:00 am - 5:00 pm EST.
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 at (571) 270-3497. 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.
/KRISTINA E. LY/Examiner, Art Unit 1671 /Michael Allen/Supervisory Patent Examiner, Art Unit 1671
Prosecution Insights