DETAILED ACTION
1. The present application filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Claims 12-29 are pending upon entry of amendment filed on 5/18/26.
Claims 12-29 are under consideration in the instant application.
The instant application comprises 2 independent claims and the invention relates a fusion construct comprising an iduronate-2-sulfatase set forth in SEQ ID NO:9 and immunoglobulin that crosses a blood brain barrier.
3. Applicant’s submission of IDS filed on 5/18/26 has been considered.
4. The oath filed on 11/26/25 has been entered.
5. Applicant’s claim for domestic priority under 35 U.S.C. 119 (e) is acknowledged.
6. The new title filed on 5/18/26 has been entered.
7. Upon approval of the terminal disclaimers filed on 5/18/26, the double patenting rejections have been withdrawn (see sections 12-14 of the office action mailed on 2/18/26).
8. The following rejections remain.
9. The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
10. This application includes one or more claim limitations that use the word “means” or “step” but are nonetheless not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph because the claim limitation(s) recite(s) sufficient structure, materials, or acts to entirely perform the recited function. Such claim limitation(s) is/are means for crossing the blood brain barrier in claims 12, 13, 19, 21, 22 and 28.
Because this/these claim limitation(s) is/are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are not being interpreted to cover only the corresponding structure, material, or acts described in the specification as performing the claimed function, and equivalents thereof.
If applicant intends to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to remove the structure, materials, or acts that performs the claimed function; or (2) present a sufficient showing that the claim limitation(s) does/do not recite sufficient structure, materials, or acts to perform the claimed function. As evidenced by the following dependent claims 13 or 22, the means for crossing the blood brain barrier is interpreted as antibody, immunoglobulin or antigen binding fragment thereof.
Applicant’s response filed on 5/18/26 has been fully considered but they were not persuasive.
Applicant has provided a Table in the response and asserted that the BBB system and antibody to a receptor are well supported throughout the specification.
Unlike Applicant’s assertion, the “means” for crossing blood brain barrier is deemed limited to insulin, transferrin, insulin-like growth factor, leptin and antibody that binds to the receptor thereof, Applicant is advised to limit to such structure.
11. 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.
12. 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 of this title, 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
13. Claims 12-29 are rejected under 35 U.S.C. 103(a) as being unpatentable over U.S. Pub. 2004/0101904 (of record) in view of US Pat 5,932,211 (of record) for the reasons set forth in the office action mailed on 2/18/26.
The ‘904 publication teaches a humanized insulin receptor (HIR) antibody that may be conjugated to a drug to treat human beings in vivo. Note that the HIR antibody is especially suited for delivering neuropharmaceutical agents to the human brain across the blood brain barrier (BBB) (see [0011]). The HIR monoclonal antibody (MAb) notably binds to an extracellular portion of the human insulin receptor (see [0006]), thus addressing a recited limitation of present claims 12, 17 and 18 and readable upon “means for crossing BBB”.
The ‘904 publication also teaches that the humanized HIR monoclonal antibody (HIRMAb) IDUA fusion protein may be used to treat patients with Hunter syndrome or type I mucopolysaccharidosis (MPS), which are characterized by an L-iduronidase (IDUA) deficiency (see [0065-066]). Further, the ‘904 publication teaches that the IDUA may be attached to the humanized HIRMAb through genetic engineering and delivered across the BBB following peripheral administration. For example, the IDUA may be fused to the carboxyl terminus or amino terminus of the heavy chain of the humanized HIRMAb, as demonstrated in Figure 5 ([0037-0040]). The ‘904 publication demonstrates that the HIRMAb avidly binds to human brain capillaries, with approximately 400% per mg protein binding at 60-120 minutes of incubation (see Example 3, paragraphs [0060-0061]). Also, the humanized HIRMAb is demonstrated to be actively transported across the BBB in vivo, wherein within 2 hours the antibody was denoted within the gray matter of the brain (see Example 4, paragraph [0062]). Hence, as the substance and amount being administered (i.e., a therapeutically effective dose of a fusion antibody) is the same in both the ‘904 publication and the instant invention, administration would be expected to result in at least about 20% of the therapeutically effective dose being delivered to the brain.
Further, the ‘904 publication teaches that fusion proteins of lysosomal enzymes and antibodies have been prepared and these fusion proteins retain biological activity (see [0066]). Therefore, the IDUA enzyme portion of the fusion antibody disclosed by the '904 publication would be expected to inherently retain its enzymatic activity, and thus would be capable of catalyzing hydrolysis of induronosidic linkages in dermatan sulfate.
The disclosure of the ‘904 publication differs from the claimed invention in that it does not teach the use of iduronate 2 sulfate amino acid sequence as in SEQ ID NO:9 as in claim 12 the instant application.
The ‘211 patent teaches the use of the claimed SEQ ID NO:9 (note SEQ ID NO:2) improve half-life and improve glycosylation that may help in translocation after expression (claims, col. 5-9). The iduronate 2 sulfatase improves conditions relating to the iduronidase activity (col. 17-18).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to administer the fusion antibody comprising the HIRMAb-IDUA fusion protein, as taught by the ‘904 publication and replace IDUA with iduronate 2 sulfatase protein in treatment of Hunter’s syndrome. The claimed SEQ DI NO:9 improve glycosylation and half-life that could improve therapeutically more effective.
From the teachings of the references, it would have been obvious to one of ordinary skill in the art to combine the teachings of the references above and there would have been a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skilled in the art at the time the invention was made, as evidenced by references, especially in the absence of evidence to the contrary.
Applicant’s response filed on 5/18/26 has been fully considered but they were not persuasive.
Applicant has asserted that the prima facie obviousness has not been shown as the HIRMAb-L-iduronidase based on the Example 6 of the ‘904 publication has not been prepared or fused. The asserted [0037-0040] discloses how to prepare humanized protein but no fusion protein has been taught. IN addition, teachings based on examples 3-4 relates humanized insulin receptor antibody to radiolabeled antibody. The reliance on IDUA enzyme portion of the fusion antibody that would expect to retain enzymatic activity does not support reasonable expectation of success in making the claimed invention. The teachings of the ‘904 publication fail to teach fusion construct as the examples and teachings are based on prophetic examples that have never been prepared.
Unlike Applicant’s assertion, HIRMab is able to across the blood brain barrier (note Example 4) and this can be linked to any pharmaceutical agent as seen in [0040-0041] as well as in claim 15 to make fusion protein. Based on the teachings of the [0040-0041], the suggested Example 6 being prophetic is erred. Example 6 suggests various locations of enzyme being fused on carboxy or amino ends. Applicant is reminded that the obviousness does not require absolute predictability but reasonable expectation of success. See MPEP 2143.02. The suggestion or teachings of fusion or linking to protein or enzyme based on [0042] to improve targeting provides reasonable expectation of success in combining the references.
In addition, the deficiency is cured by the ‘211 patent by provision of the claimed SEQ ID NO:9 and the combination of the references remains obvious.
14. No claims are allowable.
15. 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.
16. Any inquiry concerning this communication or earlier communications from the examiner should be directed to YUNSOO KIM whose telephone number is (571)272-3176. The examiner can normally be reached Mon-Fri 8:30-5.
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, Misook Yu can be reached at 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Yunsoo Kim
Patent Examiner
Technology Center 1600
June 2, 2026
/YUNSOO KIM/Primary Examiner, Art Unit 1641
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