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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
DETAILED ACTION
Claims 49-58 are pending in the instant application.
Priority
This application claims priority to the provisional application 63599885 filed on 11/16/2023.
Information Disclosure Statement
The information disclosure statements (IDS) dated 1/30/2025 and 3/4/2025 comply with the provisions of 27 CFR 1.97, 1.98, and MPEP § 609. Accordingly, they have been placed in the application file and the information therein has been considered as to the merits.
Claim Interpretation
Claim 51 refers to “QS-21” which was interpreted as an extract of the Chilean soapbark tree (instant spec pg 18, para 0094). See Martin (doi: 10.1038/s41589-023-01538-5) for a more detailed chemical description.
Objections to the Claims
Claim 55 refers to the acronym “PS-20”. For enhanced clarity, please replace “PS-20” with “polysorbate-20 (PS-20)”.
Correction is required. See MPEP § 608.01(m).
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 49-58 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.
Claim 49
Claim 49 is drawn to a pharmaceutical composition comprising (i) an immunogenic carrier protein and (ii) an immunogenic peptide, wherein the peptide “is” SEQ ID NO: 2, XFRHDSG. The claim includes a structural diagram that encompasses the sequence XFRHDSGGC, which includes two more amino acid residues than are declared in SEQ ID NO: 2. In this context “is” is equivalent to “consists of”. As a result, this claim is rendered indefinite as one cannot produce a immunogenic peptide that consists of SEQ ID NO: 2 and also satisfies the limitations placed by the chemical structure drawing. Examiner recommends modifying the claim language to use the term “comprises” instead of “is” as shown below:
“A pharmaceutical composition comprising an immunogenic peptide and an immunogenic carrier protein, wherein the immunogenic peptide comprises SEQ ID NO: 2 and the immunogenic carrier protein is CRM197, and wherein the pharmaceutical composition is: [structure].”
Dependent claims 50-58 fail to cure these deficiencies, thus are also rendered indefinite.
Claim 55
Claim 55 contains the trademark/trade name SPAN-85. 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 “sorbitane trioleate” and, accordingly, the identification/description is indefinite. Dependent claims 56-58 fail to cure these deficiencies, thus are also rendered indefinite.
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 49-58 are rejected under 35 U.S.C. 103 as being unpatentable over Arumugham (US20080145373) in view of Perez (doi: 10.2174/1570159X11311050004), Stefanetti (doi: 10.1007/s10719-020-09930-2), and Zhang (doi: 10.3390/pharmaceutics15061756).
Claim 49
Regarding claim 49, Arumugham teaches an immunogenic conjugate comprising an Aβ peptide fragment/analogue that is conjugated via derivatized functional groups of amino acids to a carrier protein such as CRM197 (pg 1, para 0009; pg 2, para 0011). Arumugham teaches the Aβ fragment is SEQ ID NO: 3, which comprises six of the seven amino acid residues of instant SEQ ID NO: 2. Note instant residue X is pyrolyzed glutamic acid, which is represented by the letter E, when non-pyrolyzed.
instant_2 --XFRHDSG-- 7
Arumugham_3 DAEFRHDSGC- 10
******
Thus the sequence of Arumugham comprises two more amino acids on the N terminus: residues D and A, that instant SEQ ID NO: 2 does not require. Arumugham teaches also the fragment, SEQ ID NO: 32, EFRHDSG-ISQAVHAAHAEINEAGR, which does not include the N-terminal DA residues (pg 6, para 0059). Thus indicating that Arumugham was aware that the DA residues were not necessary for the peptide to be immunogenic. Arumugham also terminated the Aβ fragments with a cysteine residue (e.g. SEQ ID NO: 1-9) as a means of attaching the fragment to CRM197 (pg 8, para 0064; pg 8, para 0067; pg 12, para 0101). Arumugham teaches that immunogenic fragments can be coupled to carrier proteins (i.e. CRM197) using crosslinkers such as maleimido-sulfhydryl structures (pg 13, para 0108-0110).
In sum, Arumugham teaches every limitation except the pyroglutamate (residue X, circled) nor the linker intervening the cysteine residue and the CRM197 carrier protein (boxed), as shown in the diagram below.
PNG
media_image1.png
310
1356
media_image1.png
Greyscale
Perez teaches pyroglutamate-modified Aβ peptides have been demonstrated to be the predominant components among all N-terminal truncated Aβ species in the Alzheimer’s Disease (AD) brain (pg 491, col 2, para 2). Perez teaches Aβ immunogens that comprise a pyroglutamate group induce the synthesis of antibodies that are specific to the pathological species of Aβ (pg 494, col 2, para 1).
Stefanetti teaches that a lysine residue on CRM197 can be conjugated using N-(6-N-Succinimidyl 6-Maleimidohexanoate (a.k.a. EMCS), to generate the compound shown below (Fig 2), which comprises a maleimido group for facile conjugation to a cysteine residue (arrow).
PNG
media_image2.png
517
907
media_image2.png
Greyscale
While the length of the aliphatic chains of Stefanetti differs from that instantly claimed. These differences will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating that the length of these carbon chains is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In the instant case, applicant has not provided any evidence of criticality, thus arriving at these particular aliphatic linker lengths is considered a matter of routine experimentation. See MPEP § 2144.05(II)(A).
It would have been obvious to combine the teachings of Arumugham, Perez, and Stefanetti, because (1) Arumugham supplies the same immunogenic Aβ peptide as instantly claimed and conjugates it to the carrier protein CRM197 as a means of treating a neurological disease; (2) Perez teaches that Aβ peptide fragment comprising pyroglutamate generate more effective antibodies that target the pathological forms of Aβ necessary for treating disease; and (3) Stefanetti supplies a linker that is know to be effective for attaching cysteine-containing peptides to CRM197. One of skill in the art would have had a reasonable expectation of success because (i) the instantly claimed peptide was known to be an effective immunogen as taught by Arumugham; (ii) Perez teaches such immunogens could be made more effective by including a pyroglutamate residue; and (ii) both Arumugham and Stefanetti teach that CRM197 can be conjugated to the immunogen using a maleimido unit that is reactive to a cysteine residue on the peptide. Absent the evidence for the criticality for the particular number of carbons or the particular combination of the pieces of this conjugate, the instantly claimed invention is rendered obvious over the combination of references.
Claim 50-51, 55
Regarding claims 50-51 and 55, Arumugham teaches the composition may comprise a pharmaceutically acceptable adjuvant, such as squalene (pg 16, para 0144) or cholesterol (pg 15, para 0139).
Claim 52, 56
Regarding claims 52 and 56, Arumugham teaches the composition may comprise an aluminum-based adjuvant (pg 16, para 0144).
Claim 53 and 57
Regarding claims 53 and 57, Arumugham teaches the aluminum-based adjuvant is optionally an aluminum salt (pg 16, para 0144).
Claim 54 and 58
Regarding claims 54 and 58, Arumugham does not teach the aluminum-based adjuvant is AAHS.
Zhang teaches amorphous aluminum hydroxyphosphate sulfate (AAHS) as being an effective adjuvant capable of stimulating the immune system when co-injected with vaccine formulations (pg 14, para 2).
It would have been obvious to combine the teachings of Arumugham, Perez, Stefanetti, and Zhang because (a) Arumugham, Perez, and Stefanetti supply the structure of an effective immunogenic composition as discussed above; and (b) Zhang supplies the adjuvant, AAHS, as being effective in stimulating antibody synthesis. One of skill in the art would have had a reasonable expectation of success because Arumugham teaches incorporating an aluminum-based adjuvant, and AAHS is an exemplary aluminum-based adjuvant that is known to be effective as taught by Zhang.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA ANN ESSEX whose telephone number is 571-272-1103. The examiner can normally be reached Mon - Fri 8:30-5:00.
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, Jeffrey Stucker can be reached on 571-272-0911. 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.
/L.A.E./
Examiner, Art Unit 1675
/JEFFREY STUCKER/
Supervisory Patent Examiner, Art Unit 1675
Prosecution Insights