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 .
Priority
The instant application is a continuation of International Application No. PCT/US2021/043679, filing date 07/29/2021, which claims the benefit of the prior-filed United States Provisional Patent Application No. 63/059,881, filing date 07/31/2020.
Status of Application/Claims
The preliminary amendment, filed 12/21/2023, in which claims 1-25 were modified, is acknowledged. Claims 1 and 3 are amended. Claim 26 is newly added. Claims 1-26 are currently pending and are examined on the merits herein.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/31/2023 has been fully considered by the examiner.
Specification
The use of the terms Aricept, Exelon, and Belsomra, which are trade names or marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-14 and 23-26 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon judicial exception without significantly more. The claims are drawn to naturally occurring peptides. The judicial exception is not integrated into practical application because the claims read on natural phenomena. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
The claims below are evaluated using the “Subject Matter Eligibility Test for Products and Processes” flow chart as shown in MPEP § 2106.III.
Step 1: Are the claims drawn to a process, machine, manufacture or composition of matter?
Yes. Claim 1 is drawn to a composition of matter (peptide) which is one of the four statutory categories. Claims 2-11, and 26 recite further limitations for the composition of matter (peptide). Claims 12-14 recite a composition of matter (pharmaceutical composition). Claim 23 recites a composition of matter (nucleic acid) encoding the peptide. Claim 24 recites a composition of matter (vector) comprising the nucleic acid encoding the peptide. Claim 25 recites a composition of matter (cell) comprising the vector which comprises the nucleic acid encoding the peptide.
Step 2A, Prong One: Do the claims recite an abstract idea, law of nature, or natural phenomenon?
Yes.
With respect to claim 1, SEQ ID NOs: 1, 11-12, 14, 16, and 18-19 represent amino acid fragments from the sequences of known full-length human Siglec proteins and are, thus, natural phenomena; see Uniprot.org:
P20273_human Siglec-2, residues 120-131 (applicant SEQ ID NO: 1)
Q9BZZ2_human Siglec-1, residues 116-127 (applicant SEQ ID NO: 11)P20138_human Siglec-3, residues 118-129 (applicant SEQ ID NO: 12)
O15389_human Siglec-5/14, residues 118-129 (applicant SEQ ID NO: 14)
Q9Y286_human Siglec-7, residues 123-134 (applicant SEQ ID NO: 16)
Q9Y336_human Siglec-9, residues 119-130 (applicant SEQ ID NO: 18)
Q96LC7_human Siglec-10, residues 118-129 (applicant SEQ ID NO: 19)
Claim 23 recites a nucleic acid encoding the peptide of claim 1, and is thus also considered a natural phenomenon.
Step 2A, Prong Two: Do the claims recite additional elements that integrate the judicial exception into an application?
Claim 1 recites that the peptide comprises any of SEQ ID NOs 1 or 3-20, which encode for natural peptide sequences within the natural proteins listed above.
Claims 2-3 recite additional limitations related to the percent sequence identity and length of the peptide, respectively, but do not integrate the judicial exception into a practical application.
Claims 4 and 5 recite the additional limitations related to chemical modification of the peptide but do not integrate the judicial exception into a practical application.
Claims 6-11 recite additional limitations related to the properties of the peptide sequence of claim 1 but do not integrate the judicial exception into a practical application.
Claims 12-14 recite a pharmaceutical composition comprising the peptide of claim 1 but do not integrate the judicial exception into a practical application.
Claim 23 recites a nucleic acid for the peptide of claim 1 and is a judicial exception but does not integrate the judicial exception into a practical application.
Claim 24 recites a vector comprising the nucleic acid but does not integrate the judicial exception into a practical application.
Claim 26 recites the additional limitation related to an Fc-fusion modification of the peptide but do not integrate the judicial exception into a practical application.
Step 2B: Do the claims recite additional elements that amount to significantly more than the judicial exception?
No. There are no additional recited elements that amount to more than what is found in the naturally occurring peptides (claim 1) or the nucleic acids (claim 23) that encode them.
The sequence limitations recited in claims 2 and 3 do not amount to significantly more because the sequences of claim are known at 100% identity and, thus, the claim 2-3 and 6-11 limitations describe properties of the sequences.
The chemical modifications recited in claims 4 and 5 do not amount to significantly more because these modifications are well-understood.
The pharmaceutical composition recited in claims 12-14 do not amount to significantly more because the claims recite intended uses of the known peptide and additional elements of the composition are routine in the art.
The expression vector and cell of claims 24and 25 do not amount to significantly more because vectors and cells are routinely used in making and expressing peptides, and are insignificant extra-solution elements in the protein arts.
The Fc-fusion modification recited in claim 26 does not amount to significantly more because this modification is well-understood.
Therefore, the claims encompass naturally occurring phenomena that are not markedly different in structure from naturally occurring products.
Without any evidence to the contrary, the functionality and structure of the peptides would not be markedly different from that of the naturally occurring Siglec peptides. Because there are no differences in the characteristics (structural, functional, or otherwise) between the claimed and naturally occurring molecules, the claimed invention does not have markedly different characteristics from what exists in nature. See, e.g., MPEP 2106).
Accordingly, the claim is directed to a judicial exception. Because the claim does not include any additional features that could add significantly more to the exception, the claim does not qualify as eligible subject matter under 35 U.S.C §101.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 3 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 3 is dependent on claim 1. Claim 1 requires “A peptide comprising an amino acid sequence having… SEQ ID NO: 1 or SEQ ID NO: 3-20.” These sequences are 12-mer amino acid sequences. Thus, the claim 3(a) and 3(b) limitations, “wherein the peptide is at least 11 amino acids in length” and “wherein the peptide is at least 12 amino acids in length,” respectively, render claim 3 as rejected for failing to further limit claim 1.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3 and 6-11are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Paulson et al. – US20230293711A1 (effective filing date 07/21/2020; herein referred to as Paulson), as evidenced by O’Reilly and Paulson. Multivalent ligands for siglecs. Methods Enzymol. (2010), 478, p.1-22 (herein referred to as O’Reilly).
[AltContent: textbox (Paulson, Fig.3 – alignment of human Siglec V-set domains with conserved arginine residue (arrow)
[img-media_image1.png])] Paulson teaches that Siglec proteins comprise N-terminal sialic acid ligand binding V-set domains and teaches V-set domain sequences for human “siglec” peptides that comprise instant amino acid sequences at 100% identity: Siglec-1 (SEQ ID NO: 11), Siglec-2 (SEQ ID NO: 1), Siglec-3 (SEQ ID NO: 12), Siglec-5 and Siglec-14 (SEQ ID NO: 14), Siglec-7 (SEQ ID NO: 16), and Siglec-9 (SEQ ID NO: 18), and (i.e., having at least 83% identity, having at least 91% identity, or is identical to the above applicant SEQ ID NOs; p.3, Fig.1; p.15, [0015]; p.27, [104]; instant claims 1-2a,b, 6a). Paulson’s teaches that the above sequences also comprise arginine or phenylalanine at the first or second position corresponding to applicant’s above SEQ ID NOs; and that the amino acid at the N-terminal position of the peptide is arginine or phenylalanine (p.3, Fig.1; instant claims 1-2 and 6a,b). Paulson also teaches that siglec peptides that are at least 11 amino acids in length and at least 12 amino acids in length (p.3, Fig.1; see Paulson alignment below; instant claim 3a,b).
Regarding claims 6-11: Paulson teaches the sialic acid ligand binding V-set domains for human siglecs as shown in the above figure.
Paulson does not explicitly teach that the peptide inhibits an interaction between a Siglec protein and a ligand of the Siglec protein (instant claim 6c); that the peptide competes with a peptide of SEQ ID NO: 1 or SEQ ID NOs: 3-20 for binding to a ligand of a Siglec protein (instant claim 9); that the Siglec protein is CD33 (instant claims 7 and 10); or, that the ligand of the Siglec protein is CD45 (instant claims 8 and 11). The limitations of claims 7-11 describe inherent properties for the peptide sequences of instant claim 1. Paulson’s Siglec-1, Siglec-2, Siglec-3, Siglec-5/14, Siglec-7, and Siglec-9 peptides have the same sequences as instant SEQ ID NOs: 11, 1, 12, 14, 16, and 18, respectively. Thus, Paulson’s peptides would be expected to inherently have the same properties as claimed sequences above because the sequences are substantially identical (see MPEP § 2112.01 and in re Spada).
Instant spec further evidences that SEQ ID NO: 1 (i.e., Siglec-2 peptide containing critical arginine/R) is a “peptide that mimics the sialic acid-binding domain of Siglecs” (p.5, [0027]); and, that SEQ ID NO: 1/Siglec-2 is capable of disrupting the CD33-CD45 protein/protein interaction to increase CD45 phosphatase activity, whereas a control peptide SEQ ID NO: 2/Siglec-2 peptide that does not contain the critical arginine/R did not show this effect (p.5, [0027], Fig.1; p.39, [0172]). As further disclosed by applicant specification, SEQ ID NO: 1 (i.e., Siglec-2 peptide) is considered an “inhibitory peptide” that reduces the interaction between CD33 and CD45 (p.38, [[0171]; instant claims 6c-8).
Claims 9-11 recite that the peptide of claim 1 competes with a peptide of SEQ ID NO: 1 or SEQ ID NO: 3-20 for binding to a ligand of a Siglec protein, which describes an inherent property of the claimed peptide of claim 1. As Paulson teaches siglec sialic acid binding domains that comprise instant siglec peptides, including that of Siglec-2/CD22 (i.e., instant SEQ ID NO: 1) with the critical arginine/R residue, and applicant disclosure states that the peptide structure that binds sialic acid ligand also binds to CD45 ligand and competes with CD33 to inhibit the CD33/CD45 interaction, it necessarily follows that Paulson’s Siglec-2/CD22 sialic acid binding V-set domain, which is substantially identical to that of the claims and exhibits binding to the same sialic acid/glycan as CD33 would necessarily possess the inherent characteristics of competing with CD33 for binding to both sialic acid and CD45 ligands (instant claims 9-11) and inhibiting the CD33-CD45 interaction that results in increased phosphatase activity (instant claims 6c and 7-8). Accordingly, the claims are rendered anticipated by the prior art.
Claims 1-3, 12-13, 15-20, and 22-26 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Liang et al. – WO2021091885A2 (effective filing date 11/04/2019; herein referred to as Liang).
[AltContent: textbox (Liang Siglec-9-Fc SEQ ID NO: 10 with instant SEQ ID NO: 18 (highlighted)
[img-media_image2.png])]Liang teaches siglec-9 ECD fusion peptides, as well as full length human Siglec-9, that comprise instant SEQ ID NO: 18 ( p.58, Table of sequences; also taught by Paulson as applied to claim 1 above) as well Fc domains (p.2, [010]; p.12, [060]; instant claims 1 and 26); for example, SEQ ID NO: 10 Siglec-9-Fc below:
Liang’s sequence also comprises arginine or phenyalanine at the first or second position corresponding to applicant’s above SEQ ID NO.Liang‘s siglec peptide SEQ ID NO: 10 is at least 11 amino acids in length and at least 12 amino acids in length (instant claim 3). Liang teaches pharmaceutical compositions comprising the siglec peptides that also comprise pharmaceutically acceptable excipients (p.34, [0140]; instant claims 12-13). Liang teaches administering compositions comprising the peptides for treatment of subjects with neurodegenerative disease, including Alzheimer’s disease (p.2, [008]; p.14, [079]; p.32, [0142]; p.35, [0152]; instant claims 18-19); and that the administration can be subcutaneous injection, intravenous injection, intrathecal injection, intravenous infusion, oral, or intranasal (p.38, [0176]; instant claim 19). Liang also teaches that the treatment can comprise administration of an additional therapeutic to the subject (p.34, [0151]; instant claim 20). Liang teaches the use of host cells transfected with vectors comprising nucleic acids encoding the siglec peptides (p.13, [074]; p.27, [0123]; p.29, [0126]; instant claims 23-25). Liang teaches that Siglec-9, which comprises SEQ ID NO: 18, is a type 1 immunoglobulin-like transmembrane protein expressed on immune and hematopoietic cells, including immature and mature myeloid cells, that binds sialic acid ligand via the N-terminal V-set Ig-like domain in the ECD (p.3, [003]-[004]; instant claim 6-a). Liang also teaches that all cell membranes are rich in sialic acids and that ligand binding can occur in cis and in trans (p.3, [004]). Liang also teaches that siglec peptides bind sialic acid on the surface of myeloid-derived suppressor cells/MDSCs (p.6, [015]). Further, Liang teaches siglec-9 fusion peptides harboring applicant SEQ ID NO: 18 blocked binding of other siglec proteins Siglec-3, Siglec-5, Siglec-7, Siglec-9, and Siglec-10 to the surface of MDSCs (i.e., the peptide inhibited interaction of Siglec proteins to sialic acid ligands on the membrane of MDSCs; p.50, [0221]; p.110, Fig.14; instant claims 15-16d and 22). Thus, Liang teaches a method of making a peptide that is an inhibitor of an interaction between siglec proteins and a ligand of a siglec protein (i.e. sialic acid) via synthesis of a peptide comprising the peptide of claim 1 (instant claims 6c and 22).
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 for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 4, and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Liang.
Liang teaches Siglec-9 ECD fusion peptides that comprise instant SEQ ID NO: 18 as applied to instant claim 1 above.
Liang does not explicitly teach a peptide of claim 1 that has a chemical modification (instant claim 4); or, that the chemical modification is the addition of PEG or albumin (instant claim 5).
However, Liang teaches that the Siglec-9 ECD fusion molecule can comprise a covalently-attached fusion partner, such as an Fc domain, albumin, or PEG for greater circulating half-life and improved targeting capacity (p.10, [0062]; p.27, [0121]); instant claims 4-5).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Liang by modifying the peptide to have a PEG or albumin addition, to arrive at the instantly claimed invention, in order to receive the expected benefit (also taught by Liang) that modifying the peptide would provide for greater half-life and improved targeting capacity. One of ordinary skill in the art would have a reasonable expectation of success because Liang teaches that the Siglec-9 ECD peptide fusion construct can include these modifications.
Claims 1, 12, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Liang, and further in view of American Pharmaceutical Review. Controlled release roundtable. 06/24/2020, Internet – Wayback Machine. p.1-18. (herein referred to as APR).
Liang teaches the peptide sequence for applicant SEQ ID NO: 18 as applied to instant claim 1. Liang also teaches pharmaceutical compositions comprising excipients as applied to instant claim 12 above.
Liang does not teach that the composition is formulated for extended release (instant claim 14).
APR teaches drug delivery solutions, including formulations for extended release (instant claim 14) and teaches that extended release therapeutics can serve patients who are averse to taking medications and provides the benefit of less discomfort than weekly injections (p.1, 13; instant claim 14).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Liang and APR by modifying the pharmaceutical compositions comprising the peptide and an excipient (as taught by Liang) to be formulated for extended release (as taught by APR) to arrive at the instantly claimed invention, in order to receive the expected benefits of serving patients who are averse to taking medication and to provide for less discomfort (as taught by APR).
Claims 1, 12, 18, 20 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Liang as applied to claims 1, 12, 18, and 20 above, and further in view of Alzheimer’s Association. Medications for memory. 07/14/2019, Internet – Wayback Machine. p.1-8 (herein referred to as AA).
Liang teaches the peptide sequence for applicant SEQ ID NO: 18 as applied to instant claim 1. Liang also teaches pharmaceutical compositions for treatment of neurodegenerative disease, including Alzheimer’s disease, as applied to instant claims 12 and 18-19) above. Liang further teaches that the treatment can comprise additional therapeutics as applied to instant claim 20.
Liang does not teach that the additional therapeutic is donepezil or rivastigmine (i.e., cholinesterase inhibitors), or memantine (instant claim 21).
AA teaches medications for Alzheimer’s disease that include cholinesterase inhibitors, including donepezil and rivastigmine, which are used to treat symptoms related to memory, thinking, language, judgment, and other thought processes (p.2; instant claim 14); medications that include memantine for Alzheimer’s which is used to improve memory, attention, reason, language and the ability to perform simple tasks (i.e., these treatments improve cognitive function; instant claim 21).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Liang and AA by modifying the pharmaceutical compositions comprising the peptide, an excipient, and an additional therapeutic (as taught by Liang) by including cholinesterase inhibitors (such as donepezil or rivastigmine) or memantine (as taught by AA) to arrive at the instantly claimed invention, in order to receive the expected benefits of treating symptoms associated with Alzheimer’s and to improve cognitive function (as taught by AA). One of ordinary skill in the art would have a reasonable expectation of success because Liang teaches additional therapeutics can be used in the pharmaceutical composition for treatment.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jami M Gurley whose telephone number is (571)272-0117. The examiner can normally be reached Monday - Friday, 8am - 4pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached at 571-272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JAMI MICHELLE GURLEY/Examiner, Art Unit 1647
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693