DETAILED ACTION
Status of Application, Amendments and/or Claims
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The claim listing filed on 12/9/25 has been entered; no amendments are indicated. Claims 1-3, 7, 9-11, 13-15, 17-20, 23-27 and 31-56 are pending.
Election/Restrictions
Applicants' election without traverse of Group I, claims 1-3, 7, 9, 11, 13-15, 17-20, 23-27, 31-34 and 51-53, in the reply filed on 12/9/25 is acknowledged. Claim 10 was inadvertently left out of the inventive groups listed in restriction requirement mailed on 10/10/25, but is also part of Group I. Claims 35-50 and 54-56 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The following elections without traverse of species of disorder are also acknowledged: (1) first and second peptides: PDNEAY (SEQ ID NO: 19) for each; (2) carrier: CRM197; (3) multiple antigen presenting system: helper T-cell epitopes; (4) adjuvant: QS-21; and (5) alpha-synucleinopathy: Parkinson’ disease. Claim 10 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claims 1-3, 7, 9, 11, 13-15, 17-20, 23-27, 31-34 and 51-53 are under consideration, as they read upon the elected species.
Claim Objections
Claims 1-3, 7, 9, 11, 13-15, 17-20, 23-27, 31-34 and 51-53 are objected to for the following informalities:
In claim 1, line 2, “a first peptide, a second peptide, an intrapeptide linker” should be “a first peptide, a second peptide, and an intrapeptide linker”.
In claim 1, line 3, “C-terminal” should be “C-terminus” or “C-terminal end”, and “N-terminal” should be “N-terminus” or “N-terminal end”.
In claim 1, line 4, “111-131of” should be “111-131 of”.
In claim 3, line 2, “consisting any” should be “consisting of any”.
In claim 7, line 4, “(SEQ ID NO: 19)” should be “(SEQ ID NO:19).
In claim 9, line 5, “(Phe-Lys )” should be “(Phe-Lys)”.
In claim 9, line 7, “Lys-Gly-LysGly” should be “Lys-Gly-Lys-Gly”.
In claim 11, line 2, “C -terminal” should be “C-terminal”.
In each of claims 25 and 34, lines 2-3 of each claim, “immune stimulating” should be “immune-stimulating”, “cell penetrating” should be “cell-penetrating”, and “radical induced” should be “radical-induced”.
Claim 26 should not use (a) without also using (b); e.g., “(a) one or more of the polypeptides of claim 1 and (b) at least one adjuvant”.
The remaining claim(s) are objected to for depending from an objected claim.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claims 7, 11, 13-15, 18, 20, 25, 27 and 34 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 pre-AIA the applicant regards as the invention.
Claim 7 is indefinite because it limits the polypeptide of claim 1 to a group that, in the alternative, includes the sequence “ATGFVKK”, “TGFVKKD”, or “GFVKKDQ”, but these sequences are not found within residues 111-131 as required by the parent claim.
Claims 11 and 15 are indefinite because each refers to “the peptide” of claim 1, but claim 1 includes two peptides, a first and a second peptide, and it is unclear which is being referred to by “the peptide”.
Claim 14 is directed to “The peptide of claim 11”, but this is indefinite because claim 11 is directed to “The polypeptide of claim 1” rather than to a peptide.
Claim 14 is also indefinite because it is unclear whether the “C-terminal cysteine (C)” of the linker is at the C-terminus of the peptide or the C-terminus of the linker itself.
Claim 18 recites the limitation “the one or more peptides” in lines 2-3. There is insufficient antecedent basis for this limitation in the claim. Specifically, parent claim 17 refers to “one or more of the polypeptides” but not “one or more of the peptides” and thus does not provide antecedent basis for the recitation in the dependent claim.
Claim 20 is indefinite because the carrier is further limited to a group of carriers that are joined by “and”, and thus it is unclear whether the carrier is to comprise one or all of the carriers. Furthermore, it is unclear whether the carrier to comprise one or multiple “serum albumins” and “immunoglobulin molecules”.
In claim 20, line 4, the word “and” between OMPC and HiD makes it unclear whether the carrier must comprise both of these proteins together, or only one.
In claims 25 and 34, it is unclear what is meant by the phrase “as antigen-presenting platforms” in “self-assembling nanoparticles as antigen-presenting platforms”.
In claim 27, line 5, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 27 contains the trademarks “AddaVaxTM” and “MF59®”. Where a trademark 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 cannot be used properly to identify any particular material or product. A trademark is used to identify a source of goods, and not the goods themselves. Thus, a trademark does not identify or describe the goods associated with the trademark. In the present case, the trademark is used to identify particular adjuvants and, accordingly, the identification is indefinite.
The remaining claim(s) included in the rejection are dependent claims that depend from one of the claims rejected above, and encompass the same indefinite subject matter.
Note on Prior Art Rejection(s)
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.
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.
Claims 1, 7, 9, 11, 13, 17-20, 23-27, 31-34 and 51-53 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schenk et al, U.S. Patent Application Publication 2010/0086545, published 4/8/10. The earliest date to which the instant application claims priority is 9/17/20.
Claim 1 encompasses a polypeptide comprising first and second peptides, and an intrapeptide linker located between the C-terminal end of the first and the N-terminal end of the second, wherein each peptide is 3-10 amino acids from residues 111-131 of SEQ ID NO: 01. The specification identifies SEQ ID NO: 1 as the 140-amino acid sequence of the human alpha-synuclein protein (Table 8).
Schenk teaches agents for treatment of disease characterized by “alpha-synuclein (alpha-SN) aggregation in the brain” by inducing antibodies (¶ 61). Schenk teaches that the agent can be “a fragment of alpha-synuclein” such as amino acids “118-126 of alpha synuclein” (¶ 61), and discloses the sequence of alpha-SN as SEQ ID NO: 1, which is identical to instant SEQ ID NO: 01. Schenk further teaches that “[s]ome agents of the invention comprise a fusion protein in which a C-terminal fragment of alpha-SN is linked at its N-terminus to a carrier peptide” (¶ 205). Schenk further teaches that the carrier protein is a “heterologous carrier peptide” and that the fusion proteins that include “multiple copies of a C-terminal alpha synuclein peptide, as described above, and multiple copies of a heterologous peptide interlinked to one another” (¶ 206). As such, the teachings of Schenk include a polypeptide comprising two peptides, each having amino acids 118-126 of SEQ ID NO: 1 (which is encompassed by “3-10 amino acids from residues 111-131” of instant SEQ ID NO: 01), with a heterologous peptide interlinked between, which is encompassed by the intrapeptide linker of the instant claims. As such, the teachings of Schenk anticipate claim 1.
Claim 7 encompasses a polypeptide of claim 1 comprising an amino acid sequence of “PDNEAY” (SEQ ID NO: 19), which is the elected species under consideration. These amino acids correspond to residues 120-125 of the alpha-synuclein sequence of SEQ ID NO: 01. The fragment of alpha-synuclein of amino acids 118-126 of SEQ ID NO: 1 taught by Schenk comprises residues 120-125, and thus meets the further limitations of claim 7. As such, the teachings of Schenk also anticipate claim 7.
Claim 9 encompasses a polypeptide of claim 1 wherein the intrapeptide linker comprises the amino acids valine-alanine (VA). Schenk further teaches that the heterologous peptides of the invention include a pan DR epitope, or PADRE (¶ 208), and further teaches that a preferred PADRE sequence is SEQ ID NO: 12, which includes in its sequence the amino acids valine-alanine (¶ 199). As such, the teachings of Schenk also anticipate claim 9.
Claims 11 and 13 encompass a polypeptide of claim 1, further comprising a linker to a carrier at a C-terminal portion of the peptide (claim 11), and further wherein the linker comprises an amino acid sequence that is GG (glycine-glycine). The teachings of Schenk that anticipate claim 1 are directed to a heterologous carrier protein that is interlinked between copies of the alpha-syn peptide. Thus, the heterologous carrier protein is C-terminal to at least one alpha-syn peptide. Schenk further teaches that the immunogens of the invention may be linked to carriers with spacer amino acids, for example, “gly-gly” (¶ 196). As such, the teachings of Schenk also anticipate claims 11 and 13.
Claim 17 encompasses an immunotherapy composition comprising a polypeptide of claim 1. The instant specification teaches that the term “immunotherapy” refers “to the development of a beneficial humoral (antibody mediated) and/or a cellular (mediated by antigen-specific T cells or their secretion products) response directed against an alpha-synuclein peptide in a recipient” (¶ 48, published application). The agents of Schenk taught above for claim 1 are for induction of antibodies. Schenk further teaches compositions of the invention (¶ 245), as such these compositions meet the definition of an immunotherapy composition of the instant application. As such, the teachings of Schenk also anticipate claim 17.
Claims 18-20 encompass a composition of claim 17 that further comprises a linker to a carrier at a C-terminal portion of the polypeptide (claim 18) and wherein the linker comprises the amino acid sequence GG (glycine-glycine) (claim 19) or wherein the carrier comprises diphtheria toxoid (claim 20). The teachings of Schenk that anticipate claim 1 are directed to fusion proteins that comprise multiple interlinked copies of an alpha-syn fragment and a heterologous peptide, and thus include at least one of the heterologous peptides joined to the C-terminus of the alpha-syn fragment. Schenk further teaches that the immunogens of the invention may be linked to carriers with spacer amino acids, for example, “gly-gly” (¶ 196). Schenk further teaches that carriers of the invention include diphtheria toxoids (¶ 196). As such, the teachings of Schenk also anticipate claims 18-20.
Claim 23 encompasses a composition of claim 17 further comprising a pharmaceutically acceptable diluent. Schenk further teaches that composition of the invention may comprise a pharmaceutically-acceptable diluent (¶ 254). As such, the teachings of Schenk also anticipate claim 23.
Claims 24 and 25 encompass a composition of claim 17 further comprising a multiple antigen presenting system (MAP) (claim 24) that is a Lys-based dendritic scaffold. Schenk further teaches that fusion proteins of the invention can be multimers of the form MAP4 (¶ 208-209), which is a MAP that is a Lys-based dendritic scaffold. As such, the teachings of Schenk also anticipate claims 24 and 25.
Claims 26, 27 and 31 encompass a pharmaceutical composition comprising a polypeptide of claim 1 and an adjuvant (claim 26) and further where the adjuvant is QS-21 (claim 27) or comprises a liposomal formulation (claim 31). Schenk further teaches compositions of the invention, and that such may include adjuvants (e.g., at ¶ 245, 250) and that adjuvants include QS-21 (¶ 253) or liposomal formulations that act as adjuvants (¶ 255). As such, the teachings of Schenk also anticipate claims 26, 27 and 31.
Claims 32-34 limit the composition of claim 26 in the same manner as claims 23-25 limit the composition of claim 17, and are anticipated by the further teachings of Schenk for the same reasons as set forth above.
Claims 51-53 encompass an immunization kit comprising the immunotherapy composition of claim 17 (claim 51) that further comprises an adjuvant (claim 52) and further wherein the composition is a first container and adjuvant is in a second container (claim 53) . The teachings of Schenk that anticipate the composition of claim 17 are set forth above. Schenk further teaches kits that comprise agents of the invention (¶ 134), which include the composition of the invention. Schenk further teaches that kits of the invention may include “other adjuvants” (¶ 134). Schenk further teaches that two or more agents can be administered, and may be in separate containers (¶ 134). As each agent may be composition comprising an adjuvant, this meets the limitation of claim 53 that a composition is in one container and an adjuvant is in another container. As such, the teachings of Schenk also anticipates claims 51-53.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were effectively filed 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 at the time a later invention was effectively filed in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-3, 7, 9, 11, 13-14, 17-20, 23-27, 31-34 and 51-53 are rejected under 35 U.S.C. 103(a) as being unpatentable over Schenk et al, U.S. Patent Application Publication 2010/0086545, published 4/8/10, and further in view of Fischer et al, U.S. Patent 9,777,045, published 10/3/17 (cited previously).
The scope of claim 1 is as described above. Schenk teaches agents for treatment of disease characterized by “alpha-synuclein (alpha-SN) aggregation in the brain” by inducing antibodies (¶ 61). Schenk teaches that the agent can be “a fragment of alpha-synuclein” such as amino acids “118-126 of alpha synuclein” (¶ 61), and discloses the sequence of alpha-SN as SEQ ID NO: 1, which is identical to instant SEQ ID NO: 01. Schenk further teaches that agents may include “multiple copies of a C-terminal alpha synuclein peptide” (¶ 206).
Fischer teaches that the immunogenic potential of an antigen can be enhanced by repeating the sequence one or more times in a vaccine (col 8, line 55-58). Fischer further teaches structures for such, including the structure “A+A”, which is “two identical copies of a single antigen” (col 28, line 50). Fischer further teaches that “”spacer” amino acids” of 1-10 amino acids can be placed between (col 51, lines 45-55).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to take a peptide as taught by Schenk and construct a polypeptide of the structure “A + A” as taught by Fischer and further having spacer amino acid(s) between the repeated sequence as taught by Fischer. The person of ordinary skill in the art would have been motivated to increase the immunogenic potential of the peptide taught by Schenk, and would have had a reasonable expectation of success in making the sequence because it simply requires joining two copies of the known sequence together with an amino acid spacer. This rationale supports a prima facie conclusion of obviousness in accord with KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (2007).
Claim 2 encompasses a polypeptide of claim 1 that comprises a C-terminal cysteine. Schenk further teaches that agents of the invention can be linked to carriers “to form a conjugate that helps elicit an immune response” (¶ 196). Fischer also teaches that the antigenic compositions of the invention may be conjugated to one or more carriers (col 38). Fischer teaches that conjugation can be made via sSMCC (col 40), via a cysteine added to the C-terminus of the peptide (col 42). Thus, it would have further been obvious to add a C-terminal cysteine to the polypeptide of claim 1 that is obvious over the teachings of Schenk in view of Fischer, for the purpose of conjugation to a carrier via sSMCC.
Claims 3 and 7 encompass a polypeptide of claim 2 (claim 3) or claim 1 (claim 7) that comprises an amino acid sequence of “PDNEAY” (SEQ ID NO: 19), which is the elected species under consideration. These amino acids correspond to residues 120-125 of the alpha-synuclein sequence of SEQ ID NO: 01. The fragment of alpha-synuclein of amino acids 118-126 of SEQ ID NO: 1 taught by Schenk comprises residues 120-125, and thus meets the further limitations of claims 3 and 7. As such, the polypeptide of claim 1 that is obvious over the teachings of Schenk in view of Fischer also meets the limitations of claims 3 and 7.
Claim 9 encompasses a polypeptide of claim 1 wherein the intrapeptide linker comprises the amino acids valine-alanine (VA). Schenk further teaches that the heterologous peptides of the invention include a pan DR epitope, or PADRE (¶ 208), and further teaches that a preferred PADRE sequence is SEQ ID NO: 12, which includes in its sequence the amino acids valine-alanine (¶ 199). Schenk further teaches that such heterologous peptides can be interlinked between the immunogenic peptides of the invention (¶ 206). As such, it would have further been obvious to include such a sequence as part of the spacer in the polypeptide of claim 1 that is obvious over the teachings of Schenk in view of Fischer, and such a further modified polypeptide would meet the limitations of claim 9.
Claims 11, 13 and 14 encompass a polypeptide of claim 1 that further comprises a linker to a carrier at a C-terminal portion (claim 11), and further wherein the linker comprises an amino acid sequence that is GG (Gly-Gly) (claim 13) or comprises a C-terminal cysteine (C). Schenk further teaches that the immunogens of the invention may be linked to carriers with spacer amino acids, for example, “gly-gly” (¶ 196). Fischer further teaches that the added cysteine is separated from the antigenic peptide “with a distance of at least one amino acid as a spacer, or linker” (col 42). Thus, it would have further been obvious to add a C-terminal cysteine as taught by Fischer separated by a Gly-Gly linker as taught by Schenk to the polypeptide of claim 1 that is obvious over the teachings of Schenk in view of Fischer, for the purpose of conjugation to a carrier via sSMCC. This would thus place the cysteine as the C-terminus of the linker to carrier, meeting the limitations of claims 11, 13 and 14.
With respect to claims 17-20 and 23-25 (immunotherapy compositions comprising the polypeptide of claim 1), claims 26-27 and 31-34 (pharmaceutical compositions comprising the polypeptide of claim1) and 51-53 (kits comprising the immunotherapy composition of claim 17), the further limitations of these immunotherapy compositions, pharmaceutical compositions and kits of claims are each taught by Schenk as set forth above. As such, it would further have been obvious to make a composition or kit including each of these limitations as taught by Schenk comprising the polypeptide encompassed by claim 1 that is obvious over the teachings of Schenck in view of Fischer, for the purposes of administering the polypeptide for immunization for treatment.
Claim 15 is rejected under 35 U.S.C. 103(a) as being unpatentable over Schenk et al, U.S. Patent Application Publication 2010/0086545, published 4/8/10, as applied to claim 1 above, and further in view of Skwarczynski et al, 2016. Chem Sci. 7: 842.
Claim 15 encompasses a polypeptide of claim 1 that further comprises a blocked amine at the N-terminus. The polypeptide encompassed by claim 1 that is anticipated by the teachings of Schenk is set forth above. Schenk does not further teach a blocked amine at the N-terminus of a polypeptide.
Skwarczynski teaches that acetylation of the N-termini is a method “to improve the metabolic stability of peptide antigens” (page 846). Such acetylation of the N-terminus is encompassed by “a blocked amine at the N-terminus” recited in claim 15 because acetylation of the N-terminus inherently results in blocking the amine group.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to take the polypeptide taught by Schenk that anticipates claim 1 as set forth above, and to further acetylate the N-terminus of the polypeptide as taught by Skwarczynski. The person of ordinary skill in the art would have been motivated to increase the immunogenic potential of the polypeptide taught by Schenk, and would have further been motivated to increase the metabolic stability of the peptide when administered, and would have had a reasonable expectation of success in making the sequence because it simply further acetylating the N-terminus, which, as taught by Skwarczynski, is routine for peptide-based antigens. This rationale supports a prima facie conclusion of obviousness in accord with KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (2007).
Claim 15 is alternately rejected under 35 U.S.C. 103(a) as being unpatentable over Schenk et al, U.S. Patent Application Publication 2010/0086545, published 4/8/10, and further in view of Fischer et al, U.S. Patent 9,777,045, published 10/3/17 (cited previously), as applied to claim 1 above, and further in view of Skwarczynski et al, 2016. Chem Sci. 7: 842.
Claim 15 encompasses a polypeptide of claim 1 that further comprises a blocked amine at the N-terminus. The polypeptide encompassed by claim 1 that is obvious over the teachings of Schenk in view of Fischer is set forth above. Neither Schenk or Fischer further teaches a blocked amine at the N-terminus of a polypeptide.
Skwarczynski teaches that acetylation of the N-termini is a method “to improve the metabolic stability of peptide antigens” (page 846). Such acetylation of the N-terminus is encompassed by “a blocked amine at the N-terminus” recited in claim 15 because acetylation of the N-terminus inherently results in blocking the amine group.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to take a peptide as taught by Schenk and construct a polypeptide of the structure “A + A” as taught by Fischer and further having spacer amino acid(s) between the repeated sequence as taught by Fischer, and to further acetylate the N-terminus of the polypeptide as taught by Skwarczynski. The person of ordinary skill in the art would have been motivated to increase the immunogenic potential of the peptide taught by Schenk, and would have further been motivated to increase the metabolic stability of the peptide when administered, and would have had a reasonable expectation of success in making the sequence because it simply requires joining two copies of the known sequence together with an amino acid spacer, and further acetylating the N-terminus, which, as taught by Skwarczynski, is routine for peptide antigens. This rationale supports a prima facie conclusion of obviousness in accord with KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (2007).
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY C HOWARD whose telephone number is (571)272-2877. The examiner can normally be reached on Monday to Friday from 9 AM to 5 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford, can be reached at telephone number (571) 272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ZACHARY C HOWARD/Primary Examiner, Art Unit 1674