DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
This office action is in response to the amendment filed on September 29, 2025. Claims 25-39 have been cancelled. New claims 41-63 have been added. Claims 24 and 40-63 are currently pending and are under examination.
Any objections or rejections not reiterated below are hereby withdrawn.
Withdrawal of Rejections
The rejection of claims 24-31 on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 9,447,401 B2 (3/5/2025 IDS document DD) is withdrawn based on the approval of a terminal disclaimer in the instant application.
The rejection of claims 24-43 on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 and 14-18 of U.S. Patent No. 10,865,400 B2 is withdrawn based on the approval of a terminal disclaimer in the instant application.
The rejection of claims 24-31 on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 and 17 of U.S. Patent No. 11,041,149 B2 (3/5/2025 IDS document DI) is withdrawn based on the approval of a terminal disclaimer in the instant application.
The rejection of claims 24-31 on the ground of nonstatutory double patenting as being unpatentable over claims 1-21, 24, and 25 of U.S. Patent No. 11,066,656 B2 (3/5/2025 IDS document DJ) is withdrawn based on the approval of a terminal disclaimer in the instant application.
The rejection of claims 24-31 on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11,952,600 B2 is withdrawn based on the approval of a terminal disclaimer in the instant application.
The rejection of claims 24-31 on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 12,037,618 B2 is withdrawn based on the approval of a terminal disclaimer in the instant application.
The rejection of claims 24-31 on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 12,104,184 B2 is withdrawn based on the approval of a terminal disclaimer in the instant application.
The rejection of claims 24-31 on the ground of nonstatutory double patenting as being unpatentable over claims 1-22, 25, and 26 of U.S. Patent No. 12,110,520 B2 is withdrawn based on the approval of a terminal disclaimer in the instant application.
The rejection of claims 24-31 on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 12,123,035 B2 is withdrawn based on the approval of a terminal disclaimer in the instant application.
The rejection of claims 24-31 on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 12,195,773 B2 is withdrawn based on the approval of a terminal disclaimer in the instant application.
The rejection of claims 24-31 on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 12,091,692 B2 is withdrawn based on the approval of a terminal disclaimer in the instant application.
The rejection of claims 24-31 on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 12,077,791 B2 is withdrawn based on the approval of a terminal disclaimer in the instant application.
The rejection of claims 24-31 on the ground of nonstatutory double patenting as being unpatentable over claims 1-22, 25, and 26 of U.S. Patent No. 12,060,590 B2 is withdrawn based on the approval of a terminal disclaimer in the instant application.
The rejection of claims 24-31 on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 12,054,758 B2 is withdrawn based on the approval of a terminal disclaimer in the instant application.
The rejection of claims 24-31 on the ground of nonstatutory double patenting as being unpatentable over claims 1-21, 24, and 25 of U.S. Patent No. 12,049,652 B2 is withdrawn based on the approval of a terminal disclaimer in the instant application.
The rejection of claims 24-31 on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 12,018,298 B2 is withdrawn based on the approval of a terminal disclaimer in the instant application.
The rejection of claims 24-31 on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 12,152,262 B2 is withdrawn based on the approval of a terminal disclaimer in the instant application.
The rejection of claims 24-31 on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 and 15-17 of U.S. Patent No. 12,264,345 B1 is withdrawn based on the approval of a terminal disclaimer in the instant application.
The rejection of claims 24-40 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn based on the amendment to the claims.
The rejection of claims 33-37 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form is withdrawn based on the amendment to cancel the claims.
The rejection of claims 25-39 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn based on the amendment to cancel the claims.
The rejection of claims 25-39 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, scope of enablement is withdrawn based on the amendment to cancel the claims.
Pending Rejections
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.
Claim 40 is 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. It is unclear how an amino acid sequence “corresponding to” to other amino acids as claimed in claim 40. What criteria is used for corresponding? Is it structural or functional attributes of the amino acids? Clarification is request about corresponding to. Further, it is unclear how claim 40 further limits the claim from which it depends, claim 24. Clarification is requested about the further limitation.
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 40 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 24 was amended to recite a modified polypeptide consisting of amino acids 38-468 of SEQ ID NO: 6, dependent claim 40 is drawn to a broader “comprises”. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 24 and 40-63 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are rejected for failing to describe the modified polypeptide consisting of amino acids 38-468 of SEQ ID NO: 6, wherein the modified polypeptide has 15 amino acid substitutions, and the 15 substitutions are substitutions located within 21 adjacent residues that include a residue that corresponds to amino acid position 354 of SEQ ID NO: 6. The dependent claims further recite what at least one of the amino acid substitutions can be in the modified polypeptide claimed.
Response to Remarks
Applicants state the examiner’s rejections are unfounded because they are premised on importing functional limitations into the claims, which is impermissible. Applicant’s further state the claims are fully supported by the specification of the instant application (19/071,092) under the legal standard set forth in Ariad v. Eli Lilly, 598 F.3d 1350 (Fed. Cir. 21010). Applicants state the breadth of the claims are commensurate in scope of the supporting disclosure. Applicants state the modified polypeptide of claim 24 is a polypeptide having 96.5% identity with amino acids 38-468 of SEQ ID NO: 6. Applicants cite table 8 p.224-251 to describe modified polypeptides.
Applicant's arguments filed September 29, 2025 have been fully considered but they are not persuasive. The MPEP states that written description for a genus can be achieved by a representative number of species within a broad genus. Claims are broadly generic to all possible modified polypeptides encompassed by the claims. The possible substitutions are enormous. The claims are rejected for failing to describe the structures of a genus of modified polypeptides where 15 amino acid residues of amino acids 38-468 of SEQ ID NO: 6 are substituted. The location of the possible modifications and the type of modifications are amended to be substitutions located within 21 adjacent residues that correspond to amino acid position 354 of SEQ ID NO: 6. The table cited refer to single amino acid mutation/substitutions in the parent PH20 hyaluronidase. The modified polypeptide with multiple substitutions including up to 15 amino acid substitutions are not described for the genus claimed.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.") Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Claim Rejections - 35 USC § 112, 1st paragraph, enablement rejection
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 24 and 40-63 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for some modified polypeptides with PH20 hyaluronidase activity that degrades hyaluronan, does not reasonably provide enablement for the genus of any modified polypeptide comprising any 15 amino substitutions within amino acids 38-374 of SEQ ID NO: 6, wherein the 15 substitutions are located within 21 adjacent residues that include a residue that corresponds to amino acid position 354 of SEQ ID NO: 6 as currently claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The claims are rejected because of undue experimentation to practice the claimed invention, because the disclosure does not direct the person having skill in the art to make and/or use the modified polypeptides as currently claimed. It is not clear how to use the genus of modified polypeptides claimed. It is unclear what the use of a modified polypeptide that has no hyaluronidase activity will be. The undue experimentation arises due to the unpredictability based on the differing conditions of starting materials, such as the genus of modified polypeptides being claimed.
Response to Remarks
Applicants state the standard for enablement is not whether a feature has explicit antecedent support in the specification. Rather, any analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable the skilled person in the pertinent art to make and use the claimed invention. MPEP 2164.01. Applicants state the factors have not been adequately considered by the examiner in view of the amended claims. Applicants state the breadth of the claims are commensurate in scope of the supporting disclosure. Applicants cite multiple tables (e.g. Tables 9 and 10) to identify modified polypeptides with substitutions at each and every one of amino acids 38-468 of SEQ ID NO: 6.
Applicant's arguments filed September 29, 2025 have been fully considered but they are not persuasive. The prior art has shown a large quantity of experimentation is often necessary to overcome the unpredictable nature of protein modification. Arming et al. (Eur. J. Biochem. 247 : 810-814 (1997) ; 3/5/3025 IDS NPL doc # HE**) disclose the modifications of hyaluronidases and the unpredictable functional response based on the structural modifications. A truncated hyaluronidase where the 36 amino acids from the carboxyl end were removed should yield a secreted polypeptide, but this modified polypeptide is not secreted when being manufactured in HeLa cells (see page 813, discussion section, 2nd paragraph). A second, larger deletion in the human protein was generated to obtain a derivative of the testis enzyme closely resembling the bee venom enzyme. The des-(341-474)-PH20 mutant terminates in the same region as the latter; in addition, only the four cysteine residues common to all these hyaluronidases are present in this fragment. However, contrary to our expectations we could not detect enzymatic activity in cells expressing des-(341-474)-PH20 mutant (see page 814, discussion section, top left paragraph ). Therefore, the unpredictability arises due to the differing conditions of starting materials, such as the genus of modified polypeptides being claimed. Consequently, there would be a large quantity of experimentation necessary to determine what modiifications can be made to what peptides to have a use. Factors releated to, The amount of direction or guidance presented: & The presence or absence of working examples: The specification provides numerous examples of modified PH20 hyaluronidase enzymes, but does not provide direction as to which modified polypeptides will result in hyaluronidase enzymes. The table cited refer to single amino acid mutation/substitutions in the parent PH20 hyaluronidase. The modified polypeptide with multiple substitutions including up to 15 amino acid substitutions are not identified for the genus claimed with any disclosed functional activity of the modified polypeptide. In consideration of the Wands factors, it is apparent that there is undue experimentation because of variability in prediction of outcome that is not addressed by the present application disclosure, examples, teaching, and guidance presented. Absent factual data to the contrary, the amount and level of experimentation needed is undue.
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 24 and 40-63 are rejected under 35 U.S.C. 101 because the claimed invention lacks patentable utility. Claims 24 and 40-63 are rejected under 35 U.S.C. 101 because the claimed invention is not supported by either a specific and substantial asserted utility or a well-established utility.
The claims are rejected because of a lack of a specific and substantial utility to practice the claimed invention, because the disclosure does not direct the person having skill in the art to make and/or use the modified polypeptides as currently claimed. It is not clear how to use the genus of modified polypeptides claimed. It is unclear what the use of a modified polypeptide that has no hyaluronidase activity. It appears the polypeptide of SEQ ID NO: 6 is a PH20 hyaluronidase, but is not claimed to have any activity or specific and substantial utility.
Claims 24 and 40-63 are also rejected under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph. Specifically, because the claimed invention is not supported by either a specific and substantial asserted utility or a well-established utility for the reasons set forth above in the scope of enablement rejection, one skilled in the art clearly would not know how to use the claimed invention.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 ANAND U DESAI whose telephone number is (571)272-0947. The examiner can normally be reached 9:30-6:00 EST.
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, Manjunath Rao can be reached at 571-272-0939. 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.
/ANAND U DESAI/Primary Examiner, Art Unit 1656