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 .
Application Status – Continued Examination Under 37 CFR 1.114
Claims 1-4 and 6-13 were previously pending.
A final rejection was mailed on 24 June 2025.
A request for continued examination under 37 CFR 1.114, including the fee set forth in
37 CFR 1.17(e), was filed in this application after final rejection. Since this application is
eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR
1.17(e) has been timely paid, the finality of the previous Office action has been
withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 27 October 2025
has been entered.
In their request for continued examination, Applicant has amended claims 6 and 7, cancelled claims 1-5 and 8-13, and added claims 16-28. Therefore, claims 6-7 and 14-28 are pending and currently under examination.
Affidavit/Declaration under 37 CFR 1.132
Examiner acknowledges the Affidavit by Affiant Dr. Tohru Minamino (co-inventor) was received on 19 December 2025. Examiner has fully considered the Affiant’s statement and addresses its contents below.
Priority
Since an English translation of the foreign priority document has not been received, Examiner is still unable to ascertain whether said document discloses the invention for purposes of priority. Consequently, the effective filing date for applying prior art is July 7, 2020 (the date PCT/JP2020/026560 was filed).
Objections to the Specification
The disclosure is objected to because it contains an embedded hyperlinks and/or other form of browser-executable code, not limited to instances at [0083] and [0097] for example. Applicant is required to delete the embedded hyperlinks and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Withdrawn Claim Rejections
In view of Applicant’s amendments to and cancellation of claims, all previous claim rejections are moot and hereby withdrawn.
New Claim Objections/Rejections
It is noted the rejected claims have been modified and therefore the following objections/rejections have been modified to reflect said amendments (e.g., cancelled claims, amendments which partially overcome the rejection, newly added claims).
Claim Objections
Claims 19 and 24 are objected to because of the following informalities:
Claims 19 and 24 recite a ‘GPNB’ protein. This is assumed to be a typographical error. Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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.
Claims 6-7 and 18-28 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.” See MPEP § 2163.02.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the Applicants were in possession of the claimed genus.
Instant claim 6 is directed to a pharmaceutical composition, comprising an effective amount of an immunity inducer and an effective amount of an adjuvant, wherein the immunity inducer comprises a peptide consisting of an amino acid represented by SEQ ID NO: 1 or 2; or an expression vector including a nucleic acid encoding SEQ ID NO: 1 or 2. Instant claim 7 is directed to a method treating an aging-related disease – Alzheimer’s disease, atherosclerosis, diabetes, frail, or premature senility – comprising administering an effective amount of an immunity inducer to a subject wherein the immunity inducer comprises a peptide consisting of an amino acid represented by SEQ ID NO: 1 or 2; or an expression vector including a nucleic acid encoding SEQ ID NO: 1 or 2. Clam 14 is drawn to a peptide-carrier protein complex comprising a peptide consisting of an amino acid represented by SEQ ID NO: 1 or 2; and a carrier protein bonded to the peptide. Applicant further claims various results of administering the pharmaceutical composition of claim 6 and peptide-carrier protein complex of claim 7.
The written description of the instant claims lacks adequate description of identified peptide variants of SEQ ID NOs: 1 and 2 whereby administration at “an effective amount” is capable of treating the claimed aging-related diseases and eliciting the responses of administration as recited in claims 19-28. Specifically, SEQ ID NO: 1 and SEQ ID NO: 2 have many different possible sequence variations and Applicant has not shown that all of the variable sequences have the therapeutic effects as required by the claims. One of skill in the art could not immediately envisage the encompassed variations of SEQ ID NOs: 1 or 2 that could produce this effect, and criteria are not set forth to allow one of skill in the art to identify such variations. There is no structure/function correlation presented, and a representative number of species for the combination is not presented in the instant disclosure.
Therefore, the specification provides insufficient written description to support the genera encompassed by the claim. Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that
“applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description' inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116.)
With the exception of the specifically named peptide used in applicants’ example one, the skilled artisan cannot envision the detailed chemical structure of the encompassed peptides. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481, 1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence.
University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that:
...To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention.” Lockwood v. American Airlines Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2datl966.
Independent claim 6 is drawn to a pharmaceutical composition comprising an effective amount of immunity inducer comprising a peptide consisting of SEQ ID NO: 1 or 2 or an expression vector including a nucleic acid encoding SEQ ID NO: 1 or 2. As discussed below, SEQ ID NOs: 1 and 2 contain variable amino acid residues that allow for significant variation in the disclosed sequence. Instant claim 15 further clarifies the immunity inducing peptide of claim 6 consists of an amino acid sequence represented by SEQ ID NO: 3, 4, 5, or 6. Finally, instant claims 18-23 claim methods involving the administration of the pharmaceutical composition of claim 6: method of inducing an immune response against GPNB [sic] protein in a subject (claim 19); method of inhibiting atheroma in a subject (claim 20); method of inhibiting metabolic dysfunction in a subject (claim 21); method of removing aging cells in a subject (claim 22); and method of inducing antibody-dependent cellular cytotoxicity associated with GPNMB in a subject (claim 23).
Independent claim 7 is a method of treating an aging-related disease, now limited to Alzheimer’s disease, atherosclerosis, diabetes, frail [sic], or premature senility, by administering an effective amount of an immunity inducer peptide consisting of SEQ ID NO: 1 or 2. Instant claim 16 further clarifies the immunity inducing peptide of claim 7 consists of an amino acid sequence represented by SEQ ID NO: 3, 4, 5, or 6.
Independent claim 14 is a peptide-carrier protein complex comprising a peptide consisting of an amino acid sequence represented by SEQ ID NO: 1 or 2 and a carrier protein bound to the peptide. Instant claim 17 further clarifies the peptide of claim 14 consists of an amino acid sequence represented by SEQ ID NO: 3, 4, 5, or 6. Finally, instant claims 24-28 claim methods involving the administration of peptide-carrier protein of claim 14: method of inducing an immune response against GPNB [sic] protein in a subject (claim 24); method of inhibiting atheroma in a subject (claim 25); method of inhibiting metabolic dysfunction in a subject (claim 26); method of removing aging cells in a subject (claim 27); and method of inducing antibody-dependent cellular cytotoxicity associated with GPNMB in a subject (claim 28).
Regarding the peptide recited in each of independent claims 6, 7, and 14, Applicant discloses the peptide consists of an amino acid sequence represented by SEQ ID NOs: 1 or 2, each of which contain variable amino acids that allow for significant variations within the disclosed amino acid sequence. In the specification, applicants indicate SEQ ID NO: 1 is at positions 63 to 71 and SEQ ID NO: 2 is at positions 150 to 159 (¶ [0029]). SEQ ID NO: 1 is 9 amino acids in length and allows for 2 wildcard selections at positions 1 and 5 as shown below:
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575
385
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SEQ ID NO: 2 is 10 amino acids in length and allows for up to 5 wildcard selections at positions 1, 3, 5, 6, and 10 as shown below:
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662
393
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Applicant has disclosed 4 sequence variations of SEQ ID NOs: 1 and 2 represented by SEQ ID NOs: 3, 4, 5, and 6. Applicant has not indicated any sort of structure-function correlation as it pertains to peptide (a) represented by SEQ ID NO: 1 or 2, when SEQ ID NO: 2 allows for variations in 5 amino acids of its 10-amino acid length. Furthermore, when the claimed invention is reduced to practice, Applicant only utilized SEQ ID NOs: 4 and 6 in vaccine creation (peptide vaccine 1 and peptide vaccine 2, respectively) to produce antibodies against the GPNMB protein ([0097]), wherein only peptide vaccine 1 was actually successful in producing significantly higher antibody titer against GPNMB protein (see Fig. 2A). Applicant’s own example shows that slight variations in SEQ ID NOs: 1 and 2 have a direct impact on the intended effect of the peptide as evidenced by the diminished function of SEQ ID NO: 6, which is a variant of SEQ ID NO: 2. Yet, Applicant claims to use such to treat an overly broad spectrum of aging-related diseases each involving completely different physiological pathways: Alzheimer’s disease (neurodegenerative disease), atherosclerosis (cardiovascular disease); diabetes (autoimmune/metabolic disease); frail (geriatric disease); and premature senility (genetic disease). Furthermore, Applicant claims to administer such peptides as a method of inducing an immune response against GPNB [sic] protein in a subject, method of inhibiting atheroma in a subject, method of inhibiting metabolic dysfunction in a subject, method of removing aging cells in a subject, and method of inducing antibody-dependent cellular cytotoxicity associated with GPNMB in a subject.
Protein chemistry is one of the most unpredictable areas of biotechnology. This unpredictability prevents prediction of the effects that a given number or location of mutation will have on a protein. As taught by Skolnick et al. (previously cited in 10 March 2025 office action as Trends Biotechnol. 2000 Jan;18(1):34-9), sequence-based methods for predicting protein function are inadequate because of the multifunctional nature of proteins (see e.g., abstract). Further, just knowing the structure of the protein is also insufficient for prediction of functional sites (see e.g., abstract). Sequence to function methods cannot specifically identify complexities for proteins, such as gain and loss of function during evolution, or multiple functions possible within a cell (see e.g., page 34, right column). Skolnick et al. advocate determining the structure of the protein, then identifying the functionally important residues since using the chemical structure to identify functional sites is more in line with how a protein actually works (see e.g., page 34, right column).
The sensitivity of proteins to alterations of even a single amino acid in a sequence are exemplified by Burgess et al. (previously cited in 10 March 2025 office action as J. Cell Biol. 111:2129-2138, 1990) who teach that replacement of a single lysine residue at position 118 of acidic fibroblast growth factor by glutamic acid led to the substantial loss of heparin binding, receptor binding and biological activity of the protein and by Lazar et al. (previously cited in 10 March 2025 office action as Mol. Cell. Biol., 8:1247-1252, 1988) who teach that in transforming growth factor alpha, replacement of aspartic acid at position 47 with alanine or asparagine did not affect biological activity while replacement with serine or glutamic acid sharply reduced the biological activity of the mitogen. These references demonstrate that even a single amino acid substitution will often dramatically affect the biological activity and characteristics of a protein.
Further, Miosge (previously cited in 10 March 2025 office action as Proc Natl Acad Sci U S A. 2015 Sep 15;112(37): E5189-98) teach that short of mutational studies of all possible amino acid substitutions for a protein, coupled with comprehensive functional assays, the sheer number and diversity of missense mutations that are possible for proteins means that their functional importance must presently be addressed primarily by computational inference (see e.g., page E5189, left column). However, in a study examining some of these methods, Miosge shows that there is potential for incorrect calling of mutations (see e.g., page E5196, left column, top paragraph). The authors conclude that the discordance between predicted and actual effect of missense mutations creates the potential for many false conclusions in clinical settings where sequencing is performed to detect disease-causing mutations (see e.g., page E5195, right column, last paragraph). The findings in their study show underscore the importance of interpreting variation by direct experimental measurement of the consequences of a candidate mutation, using as sensitive and specific an assay as possible (see e.g., page E5197, left column, top paragraph). Additionally, Bork (previously cited in 10 March 2025 office action as Genome Research, 2000,10:398-400) clearly teaches the pitfalls associated with comparative sequence analysis for predicting protein function because of the known error margins for high-throughput computational methods. Bork specifically teaches that computational sequence analysis is far from perfect, despite the fact that sequencing itself is highly automated and accurate (p. 398, column 1). One of the reasons for the inaccuracy is that the quality of data in public sequence databases is still insufficient. This is particularly true for data on protein function. Protein function is context dependent, and both molecular and cellular aspects have to be considered (p. 398, column 2). Conclusions from the comparison analysis are often stretched with regard to protein products (p. 398, column 3). Further, although gene annotation via sequence database searches is already a routine job, even here the error rate is considerable (p. 399, column 2). Most features predicted with an accuracy of greater than 70% are of structural nature and, at best, only indirectly imply a certain functionality (see legend for table 1, page 399). As more sequences are added and as errors accumulate and propagate it becomes more difficult to infer correct function from the many possibilities revealed by database search (p. 399, paragraph bridging columns 2 and 3). The reference finally cautions that although the current methods seem to capture important features and explain general trends, 30% of those features are missing or predicted wrongly. This has to be kept in mind when processing the results further (p. 400, paragraph bridging cols 1 and 2).
One key issue is the prediction of protein function based on sequence similarity. Kulmanov et al. (previously cited in 10 March 2025 office action as Bioinformatics, 34(4), 2018, 660–668), teach that there are key challenges for protein function prediction methods (see e.g., page 661, left column). These challenges arise from the difficulty identifying and accounting for the complex relationship between protein sequence structure and function (see e.g., page 661, left column). Despite significant progress in the past years in protein structure prediction, it still requires large efforts to predict protein structure with sufficient quality to be useful in function prediction (see e.g., page 661, left column). Another challenge is that proteins do not function in isolation. In particular, higher level physiological functions that go beyond simple molecular interactions will require other proteins and cannot usually be predicted by considering a single protein in isolation (see e.g., page 661, left column). Due to these challenges, it is not obvious what kinds of features should be used to predict the functions of a protein and whether they can be generated efficiently for a large number of proteins, such as the vast genus of variations of SEQ ID NOs: 1 and 2 encompassed by the instant claims (see e.g., page 661, left column).
Given the teachings of these references that point out the limitations and pitfalls of using sequence to predict functions, and the lack of a representative number of species across the breadth of the genus, one of skill in the art would reasonably conclude that only the specifically structured peptide, and the specific combinations demonstrated in the specification, but not the full breadth of the claims, meet the written description provision of 35 USC 112(a).
MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, ‘does the description clearly allow person of ordinary skill in the art to recognize that he or she invented what is claimed’”. The courts have decided: the purpose of the “written description” requirement is broader than to merely explain how to “make and use”; the Applicant must convey with reasonable clarity to those skilled in the art, that as of the filing date sought, he or she was in possession of the invention. The invention is for purposes of the “written description” inquiry, whatever is now claimed. See Vas-Cath, Inc v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991).
Furthermore, the written description provision of 35 USC §112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993). And Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Moreover, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicants were in possession of the claimed genus. However, factual evidence of an actual reduction to practice have not been disclosed by Applicants in the specification; nor have Applicants shown the invention was “ready for patenting” by disclosure of distinguishing identifying characteristics sufficient to show that Applicants were in possession of the claimed invention at the time the application was filed.
Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that Applicant had possession of the claimed invention at the time the instant application was filed.
Claims 6-7 and 14-28 are 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 specification, while being enabled for a method of treating atherosclerosis by administering a peptide consisting of amino acid sequences of SEQ ID NO: 4, does not reasonably provide enablement treating aging-related diseases as broadly claimed to include Alzheimer’s disease, diabetes, frail, or premature senility nor does the specification reasonably provide enablement for inducing an immune response against GPNMB protein in a subject; a method of inhibiting atheroma in a subject; a method of inhibiting metabolic dysfunction in a subject; a method of removing aging cells in a subject; or a method of inducing antibody-dependent cellular cytotoxicity associated with GPNMB in a subject by administering numerous variants of a peptide allowed by SEQ ID NOs: 1 or 2. 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.
Dr. Tohru Minamino has submitted a declaration under 35 U.S.C. 1.132 to overcome this enablement rejection. However, the declaration, while showing the administration of peptide vaccine 1 (SEQ ID NO: 4) could be used to treat Alzheimer’s disease in a mouse model, the declaration is not commensurate in scope with the broadly claimed invention of using SEQ ID NO: 1 or 2, which each allow for substantial variation, to treat disease with various underlying mechanisms and induce various responses as recited in instant claims 19-28.
It is noted that MPEP § 2164.03 teaches that “the amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability of the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The amount of guidance or direction refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as how to make and use the invention in order to be enabling.”
Enablement is considered in view of the Wands factors (MPEP 2164.01 (A)). The factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is undue include, but are not limited to (In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)):
1) nature of the invention;
2) the breadth of the claims;
3) the state of the prior art;
4) the level of one of ordinary skill;
5) the level of predictability in the art;
6) the amount of direction or guidance provided by the inventor;
7) the existence of working examples; and
8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The following is an analysis of these factors in relationship to this application:
Nature of the Invention; 2) The Breadth of the Claims
Instant claim 6 is drawn to a pharmaceutical composition; instant claim 7 is drawn to a method of treating an aging-related disease wherein the disease is Alzheimer’s disease, atherosclerosis, diabetes, frail, or premature senility; and instant claim 14 is drawn to a peptide-carrier protein complex. Instant claims 19-23 and 24-28, respectively, describe method of: inducing an immune response against GPNB [sic] protein in a subject; inhibiting atheroma in a subject; inhibiting metabolic dysfunction in a subject; removing aging cells in a subject; and inducing antibody-dependent cellular cytotoxicity associated with GPNMB in a subject. Each of the independent claims involve a peptide (a) consisting of amino acid sequences represented by SEQ ID NO: 1 or 2. While Applicant has amended claim 7 to limit aging-related diseases to Alzheimer’s disease, atherosclerosis, diabetes, frail, or premature senility, the encompassed disorders are still highly heterogeneous at both the molecular and clinical level. The breadth of the claims exacerbates the complex nature of the subject matter to which the present claims are directed.
Applicants admit that the mechanism to prevent or treat these disorders/diseases is merely speculative (¶ [0045]), but could include a number of alternative mechanisms through the administration of the claimed immunity inducer such as:
The production of an antibody that is specifically bonded to GPNMB, the produced anti-GPNMB antibody is bonded to cells expressing GPNMB and acts as a neutralizing antibody, and thus the growth of cells expressing GPNMB is suppressed (¶ [0045]); or
The produced anti-GPNMB antibody is bonded to cells expressing GPNMB to induce macrophages or natural killer cells, and the cells to which the antibody is bonded are killed (¶ [0045] and p. 35 Example 1); or
The produced anti-GPNMB antibody is bonded to cells expressing GPNMB to activate the complement system, causing a series of reactions on the surface of the cell to destroy the cell (¶ [0045]).
Regarding the production of an antibody that is specifically bonded to GPNMB, while Applicant speculated that the currently claimed invention leads to this result, actual practice indicates that, of the two vaccines tested (peptide vaccine 1 and 2), only immunization with peptide vaccine 1 (comprised of SEQ ID NO: 4) produced the desired mechanism. Immunization with peptide vaccine 2 (SEQ ID NO: 6) did not lead to a significant induction of an antibody titer against said peptide.
The State of the Prior Art; 5) The Level of Predictability in the Art
While the state of the art is relatively high with regard to the treatment of specific diseases or disorders using peptide vaccines, the state of the art with regard to broadly treating the diseases and disorders listed in the instant specification is underdeveloped.
Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a single transmembrane protein. The expression of GPNMB protein was up-regulated in vascular cells of patients and mice with atherosclerosis (¶ [0002]). On the other hand, it has been reported that GPNMB protein is overexpressed in most human malignant melanoma, breast cancer, and brain tumors, and an immunity inducer containing a peptide fragment of GPNMB protein as an active ingredient or an antibody that specifically binds to GPNMB protein for the purposes of treating or preventing cancer by immunotherapy has been developed (¶ [0003]).
However, epitopes of GPNMB protein that are effective for the purpose of removing aging cells, thereby preventing or treating various diseases, are not known (¶ [0004]).
According to Malonis et al. (previously cited in 10 March 2025 office action as Chem Rev. 2020 Mar 25;120(6):3210-3229), there are many diseases for which development of a safe and effective peptide vaccine remains elusive (p. 2). A common strategy for peptide vaccine design is to utilize naturally-occurring antibodies or TCRs as a template, following the logic that if a particular epitope has already elicited a B- or T- cell response during natural disease, then it is sufficiently immunogenic to allow induction of similar responses by administration of vaccine (p. 6). However, in other cases, epitopes that elicit an immune response most favorable for mitigating the disease may not be the most immunodominant, and thus vaccination with critical epitopes may skew the immune response to yield protective responses (p. 6). Furthermore, the binding conformation that the peptide epitope adopts in the antigen-antibody complex can sometimes be important for the activity of the antibody (p. 6). In cases where epitope conformation is important, a variety of approaches have been implemented to constrain peptide epitopes which include covalent side chain-side chain crosslinking by inclusion of disulfide bonds or other covalent constraints (p. 6). Moreover, the carrier protein to which the epitope is conjugated and the adjuvant each play a role in immune response (p. 6-7).
There is much interest in peptide vaccines and Alzheimer’s Disease, one of the many aging-related diseases the instant invention claims to prevent or treat (p. 11). Extensive evidence exists that the aberrant aggregation of two proteins, Aβ and Tau, plays an important role in the pathological neurodegeneration that is the hallmark of Alzheimer’s Disease and there is much interest in the possibility that immunization with epitopes from these two proteins could result in preventative clearance of neurotoxic forms of these proteins or avoid formation of aggregates altogether (p. 11). However, the blood-brain barrier is generally inaccessible to antibodies serves as an added challenge to peptide vaccine formulation to treat Alzheimer’s Disease (p. 11).
In addition, predicting the success of a treatment for certain diseases, such as inflammatory disease, presents challenges beyond initial screening. For example, regarding autoimmune disease, according to Steinman et al. (previously cited in 10 March 2025 office action as Nat Med. 2012 Jan 6;18(1):59-65), there are no approved clinical tests that are effective at predicting the therapeutic success or toxicity of treatments for autoimmune diseases (p. 59). Further Steinman et al. teach that a single therapeutic strategy is probably not suitable for all autoimmune diseases or even for individual subsets of patients within one diagnostic category, as there may be heterogeneous biology underlying some of these clinical entities (p. 61). Steinman et al. give the example of biologics targeting TNF and its receptors, which are effective in rheumatoid arthritis, Crohn's disease and psoriasis, but which cause marked worsening of disease in multiple sclerosis (p. 60). Blumberg et al. (Nat Med.; 18(1): 35–41) teach that one of the greatest problems in translating therapies into clinical practice in autoimmunity are the numerous failures that have been the results of clinical trials (p. 2). Despite the rapid progress that has been made in understanding the immune system, most of the underlying data has come from animal models, which necessarily only partially represent what is observed in humans (p. 2-3). To compound this limitation, there exists no standardized definition of the normal human immune system, no comprehensive understanding of how this normal system is altered in autoimmune diseases and no understanding of the relationship between these immunophenotypic characteristics and either the genetic composition of the host or the environmental stimuli that either promote or protect from the development of autoimmunity (p. 1-3). It is important to remember that the claims are even broader than the field of autoimmune disorders, including diseases such as, Alzheimer’s disease (neurodegenerative disease), atherosclerosis (cardiovascular disease); diabetes (autoimmune/metabolic disease); frail (geriatric disease); and premature senility (genetic disease), which are beyond the scope of autoimmune disorders. Given the extremely broad nature of the encompasses diseases, which have variable etiology and pathology, and the teachings of Malonis et al., Steinman et al., and Blumberg et al., one of skill in the art would not be able to predict the effectiveness of the encompassed peptide vaccine in each of the claimed diseases.
The State of the Prior Art; 7) The Existence of Working Examples
The instant specification provides one example related to a peptide vaccine targeting the GPNMB protein. Specifically, applicants disclosed peptide vaccine 1, which includes the amino acid sequence represented by SEQ ID NO: 4, and peptide vaccine 2, which includes the amino acid sequence represented by SEQ ID NO: 6 (¶ [0098]). The two vaccines, peptide vaccines 1 and 2, were conjugated with Titer Max Gold adjuvant and KLH as a carrier protein and administered to mice (¶ [0098]). Example 1 demonstrates the treatment of mice with peptide vaccine 1 significantly decreased the development of atheroma and decreased GPNMB-dependent luciferase activity in the aorta (¶ [0113]).
The working examples and declaration, together, demonstrate administration of peptide vaccine 1, comprised of SEQ ID NO: 4, Titer Max Gold adjuvant, and KLH carrier protein, and peptide vaccine 2, comprised of SEQ ID NO: 6, Titer Max Gold adjuvant, and KLH carrier protein to mice. No other compounds were administered to any subject in any other combination, or to treat any other disease or disorder. One of ordinary skill in the art would therefore be required to first, identify a combination of peptide epitope, adjuvant, and carrier protein, that have a specific effect on the body, then demonstrate which doses would result in a therapeutically effective dose. Finally, the skilled artisan would be required to experimentally identify which diseases or disorders could be treated with the combination therapy selected. This amounts to undue experimentation.
In conclusion, the claimed invention does not provide enablement for the entire scope of encompassed compositions and methods for prevention and treatment of all the aging-related diseases and disorders. Thus, for the reasons outlined above, the specification is not considered to be enabling for one skilled in the art to make and use the claimed invention as the amount of experimentation required is undue, due to the broad scope of the claims, the lack of guidance and working examples provided in the specification. Therefore, the specification is not representative of the instant claims and the specification is not fully enabled for the instant claims. In view of the above, one of skill in the art would be forced into undue experimentation to practice the claimed invention.
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 6, 7, and 14-28 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.
The claims at issue are rejected for indefiniteness for the following reasons:
Claims 6-7 and 14-17 recite the term ‘peptide (a).’ When the prior set of claims recited multiple peptides (specifically peptide a and peptide b), this connotation was appropriate. However, without multiple peptides recited, it becomes unclear what (a) represents and should be removed.
Claims 6, 7, and 14-28 either recite SEQ ID NO: 2 or depend from a claim that does. SEQ ID NO: 2 contains wildcard residues at positions 1, 3, 5, 6, and 10 as shown below. However, Applicant indicates the wildcard residue at position 10 is arginine or glycine, but then also indicates the wildcard residue at position 10 can be any naturally occurring amino acid. One of ordinary skill could not determine the metes and bounds of this claimed sequence and therefore, the claims at issue are indefinite.
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Claim 18 contains the trademark/trade names Montanide and Cervarix. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe an adjuvant and, accordingly, the identification/description is indefinite.
Conclusion
Claims 6-7 and 14-28 are rejected. No claim is allowed.
Communication
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/JULIA A ROSSI/Examiner, Art Unit 1644
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643