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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 September 9, 2025, has been entered.
Election/Restrictions
Applicant’s election without traverse of Group I (i.e., claims 1-5, 7, 9, 11-12, 14, 17-21, 23, and 39 drawn to a polypeptide molecules comprising a self-assembling polypeptide linked to a random polypeptide) in the reply filed on August 26, 2024, is acknowledged. Additionally, Applicant’s election without traverse of Species A (i.e., a single and specific polypeptide molecule as SEQ ID NO: 1 as a self-assembling polypeptide, SEQ ID NO: 85 (KEYA)20 as a random polypeptide, and SEQ ID NO: 68 as a spacer); and Species B (i.e., multiple sclerosis as a single and specific inflammatory condition) in the reply filed on August 26, 2024, is acknowledged.
Please note that the self-assembling polypeptide has been expanded to include instant SEQ ID NO: 57 and the random polypeptide has been expanded to include where “n” in (X)n is 8-20 in Species A.
Also, please note that in light of Applicants’ amendments, claim 43 is hereby rejoined and examined.
Status of Claims
Claims 1-39 were originally filed on November 2, 2021.
The amendment received on November 2, 2021, canceled claims 6, 8, 10, 13, 15-16, 22, 25-31, 33-35, and 37-38; and amended claims 3-5, 7, 9, 11-12, 14, 18, 20, 23-24, 32, 36, and 39. The amendment received on March 10, 2025, canceled claims 2-3, 7, and 9; amended claims 1, 14, 17-19, 32, and 36; and added new claims 40-43. The amendment received on August 8, 2025, amended claims 1 and 21.
Claims 1, 4-5, 11-12, 14, 17-21, 23-24, 32, 36, and 39-43 are currently pending and claims 1, 4-5, 11-12, 14, 17-21, 23, and 39-43 are under consideration as claims 24, 32, and 36 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on November 2, 2021.
Priority
The present application claims status as a 371 (National Stage) of PCT/US2020/031351 filed May 4, 2020, and claims priority under 119(e) to U.S. Provisional Application No. 62/841,972 filed on May 2, 2019.
Sequence/Claim Interpretation
For claims 1 and 21, it is noted that the Examiner is interpreting the scope of the claim with respect to the polypeptide molecule or second polypeptide molecule as comprising encompassing any unrecited components. Pursuant to MPEP 2111.03, the transitional phrase "consisting essentially of" limits the scope of a claim to the specified materials or steps "and those that do not materially affect the basic and novel characteristic(s)" of the claimed invention. In re Herz, 537 F.2d 549, 551-52, 190 USPQ 461, 463 (CCPA 1976) (emphasis in original). "A ‘consisting essentially of’ claim occupies a middle ground between closed claims that are written in a ‘consisting of’ format and fully open claims that are drafted in a ‘comprising’ format." PPG Industries v. Guardian Industries, 156 F.3d 1351, 1354, 48 USPQ2d 1351, 1353-54 (Fed. Cir. 1998). See also Atlas Powder v. E.I. duPont de Nemours & Co., 750 F.2d 1569, 224 USPQ 409 (Fed. Cir. 1984); In re Janakirama-Rao, 317 F.2d 951, 137 USPQ 893 (CCPA 1963); Water Technologies Corp. vs. Calco, Ltd., 850 F.2d 660, 7 USPQ2d 1097 (Fed. Cir. 1988). For the purposes of searching for and applying prior art under 35 U.S.C. 102 and 103, absent a clear indication in the specification or claims of what the basic and novel characteristics actually are, "consisting essentially of" will be construed as equivalent to "comprising." See, e.g., PPG, 156 F.3d at 1355, 48 USPQ2d at 1355 ("PPG could have defined the scope of the phrase ‘consisting essentially of’ for purposes of its patent by making clear in its specification what it regarded as constituting a material change in the basic and novel characteristics of the invention."). See also AK Steel Corp. v. Sollac, 344 F.3d 1234, 1240-41, 68 USPQ2d 1280, 1283-84 (Fed. Cir. 2003) (Applicant’s statement in the specification that "silicon contents in the coating metal should not exceed about 0.5% by weight" along with a discussion of the deleterious effects of silicon provided basis to conclude that silicon in excess of 0.5% by weight would materially alter the basic and novel properties of the invention. Thus, "consisting essentially of" as recited in the preamble was interpreted to permit no more than 0.5% by weight of silicon in the aluminum coating.); In re Janakirama-Rao, 317 F.2d 951, 954, 137 USPQ 893, 895-96 (CCPA 1963).
In the instant case, it is noted that the specification defines “consisting essentially of” as encompassing the recite materials or steps “and those that do not materially affect the basic and novel characteristic(s)” of the claimed invention (See instant, pg. 37, 6th paragraph). Moreover, the specification states that the term “consisting essentially of” as used herein should not be interpreted as equivalent to “comprising” (See instant, pg. 37, 6th paragraph). However, as will be further articulated below in the 112(b) rejection, the instant specification fails to clearly indicate what the basic and novel characteristics are and what components would materially affect the basic and novel characteristics of the claimed polypeptide molecule. Without a clear indication of what the basic and novel characteristics are and what components would materially affect those characteristics, an ordinary skilled artisan would be unable to determine the metes and bounds of the claimed polypeptide molecules with respect to what unrecited components are to be excluded. Given that it is not clear what subject matter is excluded, the Examiner is construing “consisting essentially of” as analogous to “comprising” in order to advance prosecution. Applicants are invited to explicitly point out support in the specification teaching what subject matter would materially affect the basic and novel characteristics of the claimed polypeptide molecules, e.g., coupling an antigen to a self-assembling polypeptide materially affects the ability of the self-assembling polypeptides to induce B cell responses and Th2 type T cell responses. Once such explanation is provided, the interpretation of the term can be adjusted accordingly.
With respect to the self-assembling polypeptide, the Examiner is interpreting the scope as open-ended requiring 100% identity to two components of the polypeptide molecule; namely, a first component of a polypeptide comprising 100% identity with any N- and/or C-terminal additions to SEQ ID NO: 1 (note: is 11 amino acids in length), and a second component of a polypeptide that is at least ten amino acids in length and limited to any combination of residues: Lys, Glu, Tyr and Ala, including e.g., 10 Lys residues or a combination of all 4 residues. As such, the minimum length of the polypeptide molecule is 21 amino acids, but there is no upper length limit. It is further noted that the first component is to exhibit the function of self-assembling, which is defined as a polypeptide that is able to spontaneously associate and form stable structures in solution (See instant specification, pg. 9, 3rd paragraph). Moreover, the two components are linked together, either covalently or non-covalently.
For claim 11, it is noted that the Examiner is interpreting the scope of the claim such that the amino acid sequence of the second component must be at least twenty amino acids in length. Plus, the amino acid residues of those at least twenty amino acids is any combination of the Lys, Glu, Tyr, and Ala.
For claim 12, it is noted that the Examiner is interpreting the scope of the claim such that a polypeptide spacer sequence covalently links the first and second components where the polypeptide spacer sequence must be at least three amino acids in length but less than ten amino acids in length. However, the amino acid residues of the polypeptide spacer sequence are not limited.
For claim 14, it is noted that the Examiner is interpreting the scope of the claim as closed-ended requiring 100% identity and the same length to one of the recited sequences. An ordinary skilled artisan would understand that a polyserine, polyglycine, or polyalanine sequence in claim 14 ranges in length from 3 to 9 amino acids in light of the scope of claim 12.
For claim 17, it is noted that the Examiner is interpreting the scope of the claim as open-ended requiring 100% identity to formula (X)nQ11 where X is an amino acid selected from K, E, Y, and A, and where n is an integer selected from 10-20, but with any N- and/or C-terminal additions to the N-terminus of (X)n and to the C-terminus of Q11. Moreover, it is noted that the instant specification defines (KEYA)n as equivalent to a peptide Xn where the polypeptide has a length of n amino acids and the X represents a random sequence of amino acids K, E, Y, and A (See instant specification, pg. 2, last paragraph to pg. 3, 1st paragraph). As such, for example, elected species (KEYA)20 correlates to a polypeptide with 20 amino acids and each of the 20 “X” amino acids are randomly selected from the amino acids K, E, Y, and A. It is further noted that Q11 is defined in the instant specification as being SEQ ID NO: 1 (i.e., QQKFQFQFEQQ) (See instant specification, pg. 8, 3rd paragraph; Table 1).
Also please note that claim 17 is not rejected under 35 USC 112(d) in light of the interpretation of claim 1. More specifically, although claim 1 utilizes the transitional phrase “consisting essentially of” and claim 17 utilizes the transitional phrase “comprising” with respect to the polypeptide molecule, since the Examiner is construing “consisting essentially of” in claim 1 as analogous to “comprising”, the scope of claim 17 properly further limits that of claim 1.
For claim 18, it is noted that the Examiner is interpreting the scope of the claim as indicated supra for claim 17 but where a spacer links (X)n and Q11 in the formula (X)nQ11. It is further noted that the spacer encompasses any spacer including chemical moieties, e.g., PEG, or any polypeptide spacer sequence of any length.
For claim 19, it is noted that the Examiner is interpreting the scope of the claim such that the spacer in the formula (X)n-spacer-Q11 is a polypeptide sequence where the polypeptide spacer sequence must be at least two amino acids in length but less than eleven amino acids (i.e., 2-10) in length. However, the amino acid residues of the polypeptide spacer sequence are not limited.
New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112
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 1, 4-5, 11-12, 14, 17-21, 23, and 39-43 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. In the instant case, claim 1 recites “[a] polypeptide molecule consisting essentially of a self-assembling polypeptide comprising SEQ ID NO: 1 (Q11) linked to random polypeptide at least ten amino acids in length, wherein each amino acid in the random polypeptide is independently selected from lysine, glutamic acid, tyrosine, and alanine.” Similarly, claim 21 recites that the pharmaceutical composition further comprises a second polypeptide molecule consisting essentially of a self-assembling peptide comprising SEQ ID NO: 1 linked to a peptide epitope or antigen. As discussed in the “Sequence Interpretation” section supra, the specification defines “consisting essentially of” as encompassing the recite materials or steps “and those that do not materially affect the basic and novel characteristic(s)” of the claimed invention (See instant, pg. 37, 6th paragraph). Moreover, the specification states that the term “consisting essentially of” as used herein should not be interpreted as equivalent to “comprising” (See instant, pg. 37, 6th paragraph). However, the instant specification fails to clearly indicate what the basic and novel characteristics are and what components would materially affect the basic and novel characteristics of the claimed polypeptide molecule. Thus, an ordinary skilled artisan would be unable to ascertain the metes and bounds of the claimed polypeptide molecules given that it is unclear what subject matter would be excluded from the scope of the claims as materially affecting the basic and novel characteristics of the claimed polypeptide molecules.
Pursuant to MPEP 2111.03, absent a clear indication in the specification or claims of what the basic and novel characteristics actually are, "consisting essentially of" will be construed as equivalent to "comprising." Although the instant specification states that “consisting essentially of” should be not construed as “comprising”, the Examiner is construing “consisting essentially of” as being analogous to “comprising” until clarification is provided. Also please note that claims 4-5, 11-12, 14, 17-20, 23, and 39-43 are rejected by virtue of their dependency.
Maintained/Modified Rejections
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
Claims 1, 4-5, 11-12, 14, 17-21, 23, 39, and 42 are rejected under 35 U.S.C. 103 as being unpatentable over Collier et al. US Publication No. 2016/0074509 A1 published on March 17, 2016 (cited in the IDS received on 3/11/24). Please note that the rejection has been updated in light of Applicants’ amendments.
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
For claims 1, 11-12, 14, and 17-19, with respect to a polypeptide molecule comprising a self-assembling polypeptide comprising SEQ ID NO: 1 linked to a random polypeptide at least 10 amino acids in length where each amino acid in the random polypeptide is independently selected from Lys, Glu, Tyr, and Ala as recited in instant claim 1; with respect to where the random polypeptide is at least 20 amino acids in length as recited in instant claim 11; with respect to where the self-assembling polypeptide is linked to the random polypeptide via a spacer wherein the spacer is a polypeptide and is at least 3 amino acids in length and less than 10 amino acids in length as recited in instant claim 12; with respect to where the spacer is a polypeptide of SEQ ID NO: 68 as recited in instant claim 14; with respect to where the polypeptide molecule comprises the formula (X)nQ11 where each X represents each amino acid in the random polypeptide and where n is an integer selected from 10-20 as recited in instant claim 17; with respect to where the polypeptide molecule comprises the formula (X)n-spacer-Q11 as recited in instant claim 18; and with respect to where the spacer is a two to 10 amino acid spacer as recited in instant claim 19:
Collier et al. teaches immunogenic compositions comprising a peptide fibril coupled to a plurality of antigens where the peptide fibril comprises a plurality of self-assembling peptides (See Collier specification, [0008]; claim 1). As such, a polypeptide molecule of Collier encompasses more than one self-assembling peptide. Attaching a short self-assembling amino acid sequence to a peptide epitope’s C-terminus can dramatically enhance the peptide’s immunogenicity (See Collier specification, [0141]). Examples of self-assembling peptides besides Q11 (SEQ ID NO: 1) and KFE8 (SEQ ID NO: 25) include EAK16 (SEQ ID NOs: 10-12, 34, 46, and 50) and KAE16 (SEQ ID NO: 49) (See Collier specification, [0010], [0048], [0053]; Table 1). Collier et al. teaches in Figure 1B an epitope-bearing self-assembling peptide with the amino acid sequence:
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, which is represented as SEQ ID NO: 28 (See Collier specification, [0020]; Figure 1B). SEQ ID NO: 28 constitutes a fusion of: an OVA epitope sequence ranges from residues 1-17 of SEQ ID NO: 28, a flexible polypeptide spacer sequence of SGSG, and the Q11 sequence ranges from residues 22-32 of SEQ ID NO: 28 and self-assembles into fibrillar aggregates (See Collier specification, [0010]-[0011], [0013], [0020], [0131]; Figure 1B). It is noted that Collier’s Q11 sequence is 100% identical to instant SEQ ID NO: 1, and Collier’s flexible spacer, SGSG, is 100% identical to instant SEQ ID NO: 68. Moreover, it is noted that the fact that Collier’s polypeptide molecule is amidated at the C-terminus is encompassed by the instantly claimed polypeptide molecule in light of the transitional phrase being construed as analogous to “comprising” thereby encompassing additional structural components. Thus, the teachings of Collier suggest a specific polypeptide molecule comprising a self-assembling polypeptide comprising instant SEQ ID NO: 1 linked to a second polypeptide via a spacer with the amino acid sequence of SGSG thereby satisfying the claim limitations with respect to a polypeptide molecule comprising a self-assembling polypeptide comprising SEQ ID NO: 1 as recited in instant claim 1, where the self-assembling polypeptide is linked to the random polypeptide via a spacer wherein the spacer is a polypeptide and is at least 3 amino acids in length and less than 10 amino acids in length as recited in instant claim 12, where the spacer is a polypeptide of SEQ ID NO: 68 as recited in instant claim 14, and where the spacer is a two to 10 amino acid spacer as recited in instant claim 19.
Regarding the random polypeptide component, as discussed supra, Collier et al. teaches immunogenic compositions comprising a peptide fibril coupled to a plurality of antigens where the peptide fibril comprises a plurality of self-assembling peptides (See Collier specification, [0008]; claim 1). Attaching a short self-assembling amino acid sequence to a peptide epitope’s C-terminus can dramatically enhance the peptide’s immunogenicity (See Collier specification, [0141]). As such, a polypeptide molecule of Collier encompasses more than one self-assembling peptide. Examples of self-assembling peptides besides Q11 (SEQ ID NO: 1) and KFE8 (SEQ ID NO: 25) include EAK16 (SEQ ID NOs: 10-12, 34, 46, and 50) and KAE16 (SEQ ID NO: 49) (See Collier specification, [0010], [0048], [0053]; Table 1). As such, Collier’s EAK16 and KAE16 self-assembling peptides constitute a random polypeptide of at least 10 amino acids in length where each amino acid in the random polypeptide is independently selected from Lys, Glu, Tyr, and Ala as recited in instant claim 1, constitute the instant component (X)n where each X represents each amino acid in the random polypeptide and where n is 16 as recited in instant claim 17.
Regarding linking Collier’s EAK16 and/or KAE16 self-assembling peptides to the Q11 self-assembling peptide, as discussed supra, Collier teaches a plurality of self-assembling peptides and where the self-assembling peptides include the Q11 sequence and EAK16/KAE16 sequences. Collier also teaches that more than one self-assembling peptide is present in a peptide fibril (See Collier specification, [0011]). The self-assembling peptides can comprise an immunogenic peptide or an antigen (See Collier specification, [0011]). The antigen can be covalently coupled to the N- and/or C-terminus of the self-assembling peptide (See Collier specification, [0013]) thereby encompassing where an antigen is coupled to two self-assembling peptides, i.e., antigen is coupled to the N-terminus of one self-assembling peptide and the C-terminus of the other. Therefore, given that Collier encompasses a plurality of self-assembling peptides covalently coupled to an antigen where the self-assembling peptides include the Q11 sequence and EAK16/KAE16 sequences and where the antigen is covalently coupled to the N- and C-termini of self-assembling peptides, an ordinary skilled artisan would be motivated with a reasonable expectation of success to utilize a polypeptide molecule containing two self-assembling polypeptides linked via the antigen/epitope, i.e., the antigen covalently coupled to the N- terminus of the Q11 sequence and the C-terminus of the EAK16 or KAE16 sequence. Therefore, the teachings of Collier et al. suggest the claim limitations as recited in instant claims 1 and 17.
Moreover, Collier et al. teaches that the antigen or the self-assembly peptide can be truncated and replaced by short linkers or they can be conjugated by linkers (See Collier specification, [0098]). The antigen or the polypeptide include one or more peptide linkers ranging in length from two to fifteen amino acids (See Collier specification, [0098]). As such, the broadest reasonable interpretation of Collier (i.e., the polypeptide includes one or more peptide linkers) encompasses where the peptide fibril comprising a plurality of self-assembling peptides such as EAK16, KAE16 and Q11 are linked via peptide linkers where the peptide linkers range in length from 2-15 amino acids, which overlaps with the instantly claimed spacer length of 2-10 amino acids. Thus, the teachings of Collier et al. suggest a peptide fibril comprising EAK16 and/or KAE16 linked to Q11 via a peptidic linker ranging in length from 3-10 or 2-15 amino acid residues such as SGSG as recited claims 12, 14, and 18-19.
Regarding where n is 20, Collier et al. teaches that the self-assembling peptides can have a length of 50 residues or less including a specific embodiment where the length of the peptide is 20 residues (See Collier specification, [0049]). Collier et al. also teaches EAK8 (SEQ ID NO: 35) and EAK12 (SEQ ID NO: 47) (See Collier specification, Table 1) thereby demonstrating self-assembling peptides contains the motif EAK where the total number of amino acids include 8, 12, and 16. As such, the length of the EAK16 and/or KAE16 peptides can be adjusted to add four amino acid residues to result in a self-assembling peptide with the sequence of EAK20. Therefore, the teachings of Collier et al. suggest elected n being 20 and the claim limitations as recited in instant claim 11.
For claims 1 and 4-5, with respect to where Q11 is a self-assembling polypeptide as recited in instant claim 1; with respect to where the self-assembling polypeptide is capable of forming nanofibers in solution as recited in instant claim 4; and with respect to where the self-assembling polypeptide assembles to form a β-sheet or an α-helix as recited in instant claim 5:
As discussed supra, Collier discloses that the Q11 sequence self-assembles into fibrillar aggregates when dissolved in water (See Collier specification, [0010], [0020], [0132]; Figure 1A). Collier also discloses that the Q11-based peptides self-assembled into β-sheet fibrils (See Collier specification, [0029]; Figure 2D]. Thus, the disclosure of Collier et al. satisfy the functional properties recited in instant claims 1 and 4-5.
Additionally, although Collier discloses that the Q11 sequence exhibits the functions of self-assembly, being capable of forming nanofibers in solution and assembles to form a β-sheet, it is unnecessary for such expressed disclosure since Collier et al. discloses the Q11 sequence thereby constituting a well-known sequence, the functional properties (i.e., self-assembly, being capable of forming nanofibers in solution and assembles to form a β-sheet) of the polypeptide as claimed and the known Q11 sequence are inherently the same. The discovery of a previously unappreciated property of a prior art composition, or a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer. Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of new functional properties (i.e., self-assembly, being capable of forming nanofibers in solution and assembles to form a β-sheet) which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 4333 (CCPA 1977). Thus, the disclosure of Collier et al. satisfy the functional properties recited in instant claims 1 and 4-5.
For claim 20, with respect to a pharmaceutical composition comprising the polypeptide molecule of claim 1 and a pharmaceutically acceptable carrier or excipient:
Collier teaches vaccines and therapeutics for use in active immunization of subjects where immunogenic compositions can include a peptide fibril coupled to a plurality of antigens, “fibril complex” (See Collier specification, [0069]). The active immunogenic ingredient is often mixed with excipients that are pharmaceutically acceptable and compatible with the active ingredient (See Collier specification, [0070]). Suitable excipients include water, saline, dextrose, glycerol, ethanol or the like or combinations thereof (See Collier specification, [0070]). Moreover, Collier teaches pharmaceutical compositions are administered to a subject that are generally dissolved or dispersed in a pharmaceutically acceptable carrier or aqueous medium (See Collier specification, [0079]). Thus, the teachings of Collier et al. satisfies the claim limitations as recited in instant claim 20.
For claim 21, with respect to where the composition further comprises a second polypeptide molecule comprising a self-assembling peptide comprising SEQ ID NO: 1 linked to a peptide epitope or antigen as recited in instant claim 21:
As discussed supra, Collier et al. teaches immunogenic compositions comprising a peptide fibril coupled to a plurality of antigens where the peptide fibril comprises a plurality of self-assembling peptides (See Collier specification, [0008]; claim 1). More than one self-assembling peptide is present in a peptide fibril (See Collier specification, [0011]). The self-assembling peptides can comprise an immunogenic peptide or an antigen (See Collier specification, [0011]). The antigen can be covalently coupled to the self-assembling peptide (See Collier specification, [0013]). The antigen can be covalently coupled to the N- and/or C-terminus of the self-assembling peptide (See Collier specification, [0013]) thereby encompassing where an antigen is coupled to two self-assembling peptides, i.e., antigen is coupled to the N-terminus of one self-assembling peptide and the C-terminus of the other. Plus, Collier teaches that the ratio of antigen to self-assembling peptide is 1:1000, 1:100, 1:10 or 1:1 (See Collier specification, [0013]) thereby suggesting that the antigen is covalently coupled to more than one self-assembling polypeptide including an embodiment of two self-assembling polypeptides. As discussed supra, Collier teaches a specific polypeptide molecule as SEQ ID NO: 28 that contains one antigen, i.e., OVA epitope, and one self-assembling polypeptide, i.e., Q11, thereby constituting a polypeptide molecule comprising a self-assembling peptide comprising SEQ ID NO: 1 linked to a peptide antigen as recited in instant claim 21. Collier also teaches in Example 1 that Collier’s SEQ ID NO: 28 formed networks of laterally entangled fibrils when it was first dissolved in water (See Collier specification, [0132]) thereby constituting a composition comprising more than one polypeptide molecule comprising a self-assembling peptide comprising instant SEQ ID NO: 1 linked to an antigen. Collier found that the relative scarcity of fibril ends suggested that the fibril length was on the order of microns (See Collier specification, [0013]) thereby constituting where the polypeptide molecules were likely fused together such that the antigen is linked to more than one self-assembling polypeptide having the amino acid sequence of instant SEQ ID NO: 1 as recited in instant claims 42-43. Therefore, when considering the teachings of Collier as a whole, Collier suggests a pharmaceutical composition that comprises more than one polypeptide molecule, i.e., a peptide fibril comprising more than one self-assembling peptide such as instant SEQ ID NO: 1 where each of these self-assembling peptides can be covalently coupled to an antigen via a linker as depicted in Collier’s SEQ ID NO: 28. Thus, the teachings of Collier suggest the claim limitation as recited in instant claim 21. Moreover, since Collier suggests where an antigen is coupled to two self-assembling peptides, i.e., antigen is coupled to the N-terminus of one self-assembling peptide and the C-terminus of the other where the ratio of antigen to self-assembling peptide encompasses 1:2, it would necessarily follow that the antigen can be linked to a second self-assembling polypeptide as recited in instant claim 42.
For claim 23, with respect to where the pharmaceutically acceptable carrier or excipient is an isotonic solution and where the self-assembling polypeptide linked to a random polypeptide forms nanofibers in solution:
As discussed supra, the pharmaceutically acceptable carrier or excipient can be saline (See Collier specification, [0070]). Thus, the teachings of Collier satisfy the claim limitation with respect to where the pharmaceutically acceptable carrier or excipient is an isotonic solution as recited in instant claim 23.
Furthermore, Collier teaches in Example 1 that the OVA-GSGS-Q11 amino acid sequence dissolved in water (See Collier specification, [0020], [0132]; Figure 1A). The Q11 formed networks of laterally entangled fibrils when it was first dissolved in water and then added to salt-containing buffers such as PBS (See Collier specification, [0020], [0132]; Figure 1A and 2) thereby constituting where the pharmaceutically acceptable carrier or excipient is an isotonic solution as recited in instant claim 23. In PBS, the polypeptide molecule appeared as long, unbranched fibrils with widths of about 15 nm (See Collier specification, [0021], [0132]; Figure 2C) thereby constituting where the formation of nanofibers in solution as recited in instant claim 23.
Additionally, although Collier teaches a specific embodiment of a polypeptide molecule containing the Q11 sequence exhibits the functions of forming nanofibers in solution, but not a specific embodiment of the formation of nanofibers when two self-assembling polypeptides are utilized, it is unnecessary for Collier et al. to teach this limitation because the functional property (i.e., forming nanofibers in solution) of the polypeptide molecule as claimed and the known polypeptide molecule are necessarily the same. The discovery of a previously unappreciated property of a prior art composition, or a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer. Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new functional property (i.e., forming nanofibers in solution) which is necessarily present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 4333 (CCPA 1977). Thus, the disclosure of Collier et al. satisfy the functional property recited in instant claim 23.
For claim 39, with respect to a kit comprising the polypeptide molecule of claim 1 and instructions for use:
Collier et al. teaches kits comprising any embodiment of the invention that can be used to achieve methods of the invention (See Collier specification, [0022]). Thus, the teachings of Collier et al. satisfies the claim limitation with respect to a kit comprising the polypeptide molecule of claim 1 as recited in instant claim 39.
Additionally, it is noted that the Federal Circuit found that in addressing a method claim whose first step was drawn to the prior art method of administering metazalone AND an additional prescribing step addressing the inherent result of taking metaxalone with food, i.e., an increase in the bioavailability of the drug, the Federal Circuit in the King Case, 95 USPQ2d at 1842-43, analogized these facts to those faced by written instructions and their effect on compositions claims: “In an analogous context, we have held that ‘[w]here the printed matter is not functionally related to the substrate, the printed matter will not distinguish the invention from the prior art in terms of patentability. Citing In re Gulack, 703 F.2d 1381, 1385 (Fed. Cir. 1983). In holding the metaxalone administering method anticipated, the Federal Circuit established the following relevant inquiry as to whether a prescribing step imparts patentability: "...whether the additional instructional limitation ... has a "new and unobvious functional relationship” with the known method of administering metaxalone with food.“ See In re Ngai, 367 F.3d at 1338 (quoting In re Gulack, 703 F.2d at 1386). As in the “King" case, the instant kit comprising instructions for use merely recite information regarding the intended use of the prior art polypeptide molecule, and not structurally limiting the polypeptide molecule. Thus, the instant instructions limitation is similarly not patentably distinguishing and merely is an informing limitation that provide no novelty to the claimed kit.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims (MPEP §2141.012)
Collier et al. does not teach a specific embodiment of a pharmaceutical composition comprising polypeptide molecule comprising a self-assembling polypeptide comprising SEQ ID NO: 1 (Q11) linked to a random polypeptide at least 10 amino acids in length where each amino acid in the random polypeptide is independently selected from Lys, Glu, Tyr and Ala and a pharmaceutically acceptable carrier as recited in instant claims 1 and 20, where the self-assembling polypeptide is linked to the random polypeptide via a spacer that is 3-9 amino acids in length such as SEQ ID NO: 68 as recited in instant claims 12 and 14, where the composition further comprises a second polypeptide molecule comprising a self-assembling peptide comprising SEQ ID NO: 1 linked to a peptide epitope or antigen as recited in instant claim 21, where the peptide epitope or antigen is linked to a second self-assembling polypeptide as recited in instant claim 42, and where the second self-assembling polypeptide comprises SEQ ID NO: 1 as recited in instant claim 43. However, the teachings of Collier et al. cure these deficiencies by constituting some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention and/or utilizing the "Obvious to try" rationale - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success pursuant to KSR.
Collier et al. does not teach a specific embodiment of polypeptide molecule comprising the formula (X)n-Q11 where each X is independently selected from K, E, Y, and A, and n is an integer from 10-20 including 20 as recited in instant claims 1, 11 and 17 and as elected, where the polypeptide molecule comprises the formula (X)n-spacer-Q11 as recited in instant claim 18; where the spacer is a 2-10 amino acid spacer as recited in instant claim 19. However, the teachings of Collier et al. cure these deficiencies by constituting some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention and/or utilizing the "Obvious to try" rationale - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success pursuant to KSR. Moreover, the amino acid spacer length taught by Collier et al. overlaps with the instantly claimed amino acid spacer length as further articulated below.
Finding of Prima Facie Obviousness Rationale and Motivation (MPEP §2142-4143)
With respect to a pharmaceutical composition comprising polypeptide molecule comprising a self-assembling polypeptide comprising SEQ ID NO: 1 (Q11) linked to a random polypeptide at least 10 amino acids in length where each amino acid in the random polypeptide is independently selected from Lys, Glu, Tyr and Ala and a pharmaceutically acceptable carrier as recited in instant claims 1 and 20, where the self-assembling polypeptide is linked to the random polypeptide via a spacer that is 3-9 amino acids in length such as SEQ ID NO: 68 as recited in instant claims 12 and 14, where the composition further comprises a second polypeptide molecule comprising a self-assembling peptide comprising SEQ ID NO: 1 linked to a peptide epitope or antigen as recited in instant claim 21, where the peptide epitope or antigen is linked to a second self-assembling polypeptide as recited in instant claim 42, and where the second self-assembling polypeptide comprises SEQ ID NO: 1 as recited in instant claim 43, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant application to follow the teachings of Collier et al. and modify an immunogenic composition comprising a plurality of Q11 self-assembling polypeptides that are covalently coupled to OVA as an antigen thereby forming the instant second polypeptide molecule of Collier’s SEQ ID NO: 28 such that the OVA epitope of SEQ ID NO: 28 is covalently linked to a second self-assembling polypeptide such as EAK12,16 or KAE16 at the OVA’s N-terminus thereby resulting in a polypeptide molecule having the amino acid sequence of EAK12,16 or KAE16/OVA epitope/SGSG linker/Q11 thereby dramatically enhancing the peptide epitope’s immunogenicity. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because coupling a peptide fibril comprising a plurality of self-assembling peptides to a plurality of antigens at the antigen’s N- and/or C-termini thereby encompassing where a self-assembling polypeptide is covalently linked to either and/or both termini of the antigen and a ratio of antigen to self-assembling polypeptide of 1:10 was known to enhance the peptide epitope’s immunogenicity; and because a plurality of self-assembling peptides were known to include EAK12, 16, KAE16 and Q11 as taught by Collier et al. One of ordinary skill in the art at the time the invention was made would have had a reasonable expectation of success given that an immunogenic composition comprising a plurality of polypeptide molecules of SEQ ID NO: 28 and a pharmaceutically acceptable carrier of Collier et al. where each polypeptide molecule contained the amino acid sequence of OVA epitope/SGSG linker/Q11, and therefore, covalently linking a second self-assembling polypeptide such as EAK12,16 or KAE16 to one of the polypeptide molecules in the composition at the OVA’s N-terminus thereby resulting in a polypeptide molecule having the amino acid sequence of EAK12,16 or KAE16/OVA epitope/SGSG linker/Q11 would support the enhancement of the peptide epitope’s immunogenicity, especially given the finite number of self-assembling peptides taught by Collier et al., by constituting some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention and/or utilizing the "Obvious to try" rationale - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success pursuant to KSR.
With respect to a polypeptide molecule comprising the formula (X)n-Q11 where each X is independently selected from K, E, Y, and A, and n is an integer from 10-20 including 20 as recited in instant claims 1, 11 and 17 and as elected, where the polypeptide molecule comprises the formula (X)n-spacer-Q11 as recited in instant claim 18; where the spacer is a 2-10 amino acid spacer as recited in instant claim 19, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to follow the teachings of Collier et al. and modify an immunogenic composition comprising a peptide fibril comprising EAK12,16 and/or KAE16 linked to Q11 via a peptidic spacer of 2-15 amino acid residues such as SGSG as a plurality of self-assembling peptides coupled to OVA and/or SIN epitopes as a plurality of antigens thereby dramatically enhancing the peptide epitope’s immunogenicity. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because coupling a peptide fibril comprising a plurality of self-assembling peptides to a plurality of antigens at the antigen’s C-termini was known to enhance the peptide epitope’s immunogenicity; because a plurality of self-assembling peptides were known to include EAK12, 16; KAE16 and Q11; and because the polypeptides were known to be conjugated via a peptidic linker of a length ranging from 2-15 amino acids such as SGSG as taught by Collier et al.
One of ordinary skill in the art at the time the invention was made would have had a reasonable expectation of success given that the coupling of a plurality of self-assembling peptides to a plurality of antigens at the antigens’ C-termini of Collier et al. were used to enhance the peptide epitope’s immunogenicity, and therefore, coupling EAK12,16 and/or KAE16 linked to Q11 via a peptidic spacer of 2-15 amino acid residues such as SGSG as a plurality of self-assembling peptides coupled to OVA and/or SIN epitopes as a plurality of antigens would support the enhancement of the peptide epitope’s immunogenicity, especially given the finite number of self-assembling peptides taught by Collier et al., by constituting some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention and/or utilizing the "Obvious to try" rationale - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success pursuant to KSR.
With respect to the amino acid spacer length as recited in instant claims 12 and 19, MPEP 2144.05(I) states that "[i]n the case where the claimed ranges "overlap or lie inside ranges discloses by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%". The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.) Moreover, the Federal Circuit found that a prima facie case existed where a claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms and the prior art taught that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." In re Geisler, 116 F.3d 1465, 1469-82, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997). Therefore, the claimed amino acid spacer length would have been obvious to one of ordinary skill in the art since the claimed range (i.e., 3-9 residues as recited in instant claim 12; and 2-10 residues as recited in instant claim 19) lies within with the prior art amino acid spacer range (i.e., 2-15 residues).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant application, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 1 and 40-41 are rejected under 35 U.S.C. 103 as being unpatentable over Collier et al. US Publication No. 2016/0074509 A1 published on March 17, 2016 (cited in the IDS received on 3/11/24) as applied to claim 1 above, and further in view of Lee et al., Adv. Sci. 6:15 pages (first available November 2018), as applied to claims 40-41 herewith.
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
For claim 1, please see discussion of Collier et al. supra.
For claims 40-41, with respect to where the random polypeptide comprises at least one tyrosine as recited in instant claim 40; and with respect to where the random polypeptide comprises at least one lysine, at least one glutamic acid, at least one tyrosine, and at least one alanine as recited in instant claim 41:
As discussed supra, Collier et al. teaches that the self-assembling polypeptide includes EAK16 (SEQ ID NOs: 10-12, 34, 46, and 50) and KAE16 (SEQ ID NO: 49). As such, Collier