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 .
DETAILED ACTION
Examiner acknowledges receipt of the reply filed 7/30/2025, in response to the non-final office action mailed 5/01/2025
Claims 1-11 and 16 are pending. Claims 1-6, 11, and 16 remain withdrawn from further consideration for the reasons made of record.
Claims 7-10 are being examined on the merits in this office action.
Drawings- withdrawn
The objection to the drawings is withdrawn in view of the amendment filed 7/30/2025.
Claim Objections- withdrawn
The objection of claims 7-9 is withdrawn in view of the amendment filed 7/30/2025.
Claim Rejections - 35 USC § 112
The rejection of claims 7-10 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in view of the amendment filed 7/30/2025.
The rejection of claims 7-9 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph (written description), is withdrawn in view of the amendment filed 7/30/2025.
Response to Arguments
Applicant’s amendment filed 7/30/2025, with respect to the above objections and rejections have been fully considered and are persuasive. The objections and rejections have been withdrawn.
Applicant's arguments and amendment filed 7/30/2025 have been fully considered but they are not persuasive with respect to the following rejections.
An action on the merits is presented herein.
Specification- maintained
Please note, the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification. MPEP § 608.01.
The objection is maintained from the office action mailed 5/01/2025, but has been amended to reflect claims filed 7/30/2025. The use of the terms, including but not limited to, Prolia, Xgeva, Rituxan, and Enbrel, which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. See as-filed specification at least at p. 20.
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.
Response to Arguments
Applicant traversed the objection at page 6 of the reply filed 7/30/2025. Examiner acknowledges that Applicant capitalized the trademarks and included a symbol. However, Applicant did not amend the specification to include a generic terminology for the respective trademarks.
The objection is maintained for at least these reasons.
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.
Claim(s) 7-10 remain/are rejected under 35 U.S.C. 103 as being unpatentable over Castrillon et al (WO 2005/007687- previously cited), and further in view of GenBank Accession No: XM_011535628.3 (March 2018)- previously cited). The rejection is maintained from the office action mailed 5/01/2025, but has been amended to reflect claims filed 7/30/2025.
Castrillon et al teach pharmaceutical compositions comprising a pharmaceutically acceptable carrier, and viral vector comprising a nucleic acid which comprises the sequence encoding a Foxo3 polypeptide. The nucleic acids can be inserted into vectors and used as gene therapy vector. The expression vectors preferably contain a nucleic acid encoding a FoxO3 protein (pp. 40-58). The Foxo3 nucleic acid sequences include Foxo3 variants and orthologs [reads on isoforms], as well as fragments (pp. 51-66).
Castrillon et al does not expressly teach a polypeptide of instant SEQ ID NO:1.
GenBank Accession No: XM_011535628.3 teaches a human forkhead box O3 variant and predicted amino acid sequence. The amino acid sequence is 453 amino acids in length and has 100% identity with instant SEQ ID NO:1. The correlated nucleic acid is also taught in the reference.
It would been obvious to one of ordinary skill in the art to modify the composition of Castrillon et al comprising a pharmaceutically acceptable carrier and a viral vector encoding a Foxo3a peptide, to include or instead use the Fox03 isoform of GenBank Accession No: XM_011535628.3. Castrillon et al expressly taught that Foxo3 polypeptide/nucleic acids included variants and fragments thereof. A person of ordinary skill in the art would have had a reasonable expectation of success in substituting the Foxo3a polypeptide of Castrillon et al with the Foxo3a isoform of GenBank Accession No: XM_011535628.3 because both were explicitly taught as being useful as fox03 polypeptides. Therefore, these compositions are functional equivalents in the art, and substituting one for the other would have been obvious at the time of the invention. “When a patent ‘simply arranges old elements with each performing the same function it had been known to perform’ and yields no more than one would expect from such an arrangement, the combination is obvious.” See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007) at 1395-1396, quoting Sakraida v. AG Pro, Inc., 425 U.S. 273 (1976) and In re Fout, 675 F.2d 297, 301 (CCPA 1982) (“Express suggestion to substitute one equivalent for another need not be present to render such substitution obvious”). The Fox03 isoform of GenBank Accession No: XM_011535628.3 has 100% identity with instant SEQ ID NO:1. The correlated nucleic acid is also taught in the reference and has identity with instant SEQ ID NO:2.
Accordingly, claims 7, 9, and 10 are rendered obvious. Regarding claim 8, Castrillon et al teach recombinant expression in viral vectors. Viral vectors include an adenoviral or AAV vector (pp. 40-41, 48-51).
Claims 7-10 are obvious in view the teachings of the cited references.
Response to Arguments
Applicant traverses the rejection at pp. 7-8 pf the reply filed 7/30/2025. Applicant states in the reply at p. 8:
PNG
media_image1.png
245
631
media_image1.png
Greyscale
Applicant further asserts that the Foxo3 isoform2 acts as a “novel osteoclastic inhibitor in bone remodeling”. Id. Applicant asserts that this biological function was previously unknown, and that neither of the cited references “provides the motivation to provide a viral vector comprising a sequence encoding this isoform”. Applicant asserts hindsight reasoning. Id.
Examiner has reviewed and considered applicant’s arguments but is not persuaded.
Examiner reiterates that GenBank Accession No: XM_011535628.3 has 100% identity with instant SEQ ID NO:1. The correlated nucleic acid is also taught in the reference and has 100% identity with instant SEQ ID NO:2.
Castrillon et al expressly taught pharmaceutical compositions comprising a pharmaceutically acceptable carrier, and viral vector comprising a nucleic acid which comprises the sequence encoding a Foxo3 polypeptide. The nucleic acids can be inserted into vectors and used as gene therapy vector. The expression vectors preferably contain a nucleic acid encoding a FoxO3 protein (pp. 40-58). The Foxo3 nucleic acid sequences include Foxo3 variants and orthologs [reads on isoforms] (pp. 51-66).
The skilled artisan merely substituted the known Foxo3 sequence of GenBank Accession No: XM_011535628.3 (correlating with the claimed Foxo3 isoform 2 sequence) with the sequences of Castrillon et al. Castrillon et al expressly taught/contemplated insertion of such isoform sequences into the viral vectors disclosed by the reference.
Examiner further notes, the U.S. Federal Circuit has explicitly stated that in order to make a prima facie case of obviousness, the suggestion and motivation to combine the references need not be explicitly stated in the text of the references. In DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 80 USPQ2d 1641 (Fed. Cir. 2006), the Court writes, “the suggestion test is not a rigid categorical rule. The motivation need not be found in the references sought to be combined, but may be found in any number of sources, including common knowledge, the prior art as a whole, or the nature of the problem itself. In re Dembiczak, 175 F.3d 994, 999 [50 USPQ2d 1614] (Fed. Cir. 1999). As we explained in Motorola, Inc. v. Interdigital Tech. Corp., 121 F.3d 1461, 1472 [43 USPQ2d 1481] (Fed. Cir. 1997), ‘there is no requirement that the prior art contain an express suggestion to combine known elements to achieve the claimed invention. Rather, the suggestion to combine may come from the prior art, as filtered through the knowledge of one skilled in the art.’” See Dystar at 1645. “Our suggestion test is in actuality quite flexible and not only permits, but requires, consideration of common knowledge and common sense.” See Dystar at 1650. See also In re Fout, 675 F.2d 297, 301 (CCPA 1982) (“Express suggestion to substitute one equivalent for another need not be present to render such substitution obvious.”). In this case, Castrillon et al taught pharmaceutical compositions comprising a pharmaceutically acceptable carrier, and viral vector comprising a nucleic acid which comprises the sequence encoding a Foxo3 polypeptide. The reference further taught expression vectors preferably contain a nucleic acid encoding a FoxO3 protein (pp. 40-58). The Foxo3 nucleic acid sequences include Foxo3 variants and orthologs [reads on isoforms] (pp. 51-66). The skilled artisan would recognize that GenBank Accession No: XM_011535628.3 taught a fox03 isoform polypeptide sequence, and nucleic acid sequence encoding the polypeptide that could be incorporated into the viral vectors taught by Castrillon et al. The motivation to incorporate the sequence of GenBank Accession No: XM_011535628.3 into the fox03 encoding viral vectors of Castrillon et al. can be found in the common knowledge of the art and common sense of its skilled practitioners.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., functional limitation of osteoclastic inhibitor in bone remodeling) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Examiner further notes that the instant claims are composition claims. Functional properties - osteoclastic inhibitor in bone remodeling- do not limit the structural sequence of the claimed nucleic acid encoding the Fox03 isoform 2 polypeptide. "Products of identical chemical composition cannot have mutually exclusive properties. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.” See In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP § 2112.01.
The rejection is maintained for at least these reasons, and those previously made of record.
Relevant Art Not Relied Upon
UnitProt Accession No. O43524 (Forkhead box protein O3. Entry July 2018, 14 pages, accessed 4/27/2025 at URL rest.uniprot.org/unisave/O43524?format=txt&versions=201- previously cited) is 673 amino acids in length and correlates with human Forkhead box protein O3. Amino acid residues 221-673 have 100% identity with instant SEQ ID NO:2. UnitProt Accession No. O43524 discusses isoform 2 which is truncated/missing amino acids 1-220. Thus, UnitProt Accession No. O43524 teaches Fox03 isoform 2 corresponds with amino acids 221-673, which is 453 amino acids in length and has 100% identity with instant SEQ ID NO:1. UnitProt Accession No. O43524 further refers to Ref Sequence XM_005266868.3 [O43524-2] (Foxo3 isoform 2) which teaches the nucleic acid sequence of SEQ ID NO:2.
Anderson et al (Genomics 47:187-199 (1998)- previously cited)) teach cloning and characterization of the Fox03 protein (also known in the art as FKHRL1) which is 673 amino acids in length. The reference teaches the nucleic acid sequence and corresponding amino acid sequence (Fig. 2). Amino acid residues 221-673 have 100% identity with instant SEQ ID NO:2.
Conclusion
No claims are allowed.
Claims 1-11 and 16 are pending. Claims 1-6, 11, and 16 are withdrawn.
Claims 7-10 are rejected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTINA M HELLMAN whose telephone number is (571)272-2836. The examiner can normally be reached M-F 9:00 am-5:30 pm.
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, LIANKO GARYU can be reached at 571-270-7367. 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.
/KRISTINA M HELLMAN/ Examiner, Art Unit 1654
/JULIE HA/ Primary Examiner, Art Unit 1654