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 October 7, 2025. Claims 25-43 have been cancelled. New claims 44-66 have been added. Claims 24 and 44-66 are currently pending and are under examination.
Any objections or rejections not reiterated below are hereby withdrawn.
Withdrawal of Rejections
The rejection of claims 24-43 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the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 12,195,773 B2 is withdrawn based on the approval of a terminal disclaimer in the instant application.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 25-43 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn based on the amendment to cancel the claims.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rejection of claims 25-43 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, scope of enablement is withdrawn based on the amendment to cancel the claims.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 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 44-66 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 3-433 of SEQ ID NO: 35, wherein the modified polypeptide has 17 amino acid substitutions with reference to amino acids 3-433 of SEQ ID NO: 35, wherein none of the substitutions are present at any of residues 25, 107-137, 170-200, 203, 242-262, 316, 333, 341, 346, 352, 358, 400, 402, 408, 423, and 429 with reference to SEQ ID NO: 35.
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 by both the legal standards under which the sufficiency of written description must be assessed. Applicants state the analysis of whether the specification complies with the written description requirements calls for the examiner to compare the scope of the claim with the scope of the description to determine whether applicant has demonstrated that the inventor was in possession of the claimed invention citing MPEP 2163. Further applicants state for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. If the genus has substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus citing MPEP 2163. Applicants quote Ariad v. Eli Lilly, 598 F.3d 1336, 1350 (Fed. Cir. 2010) to discuss sufficiency of description of a genus – “sufficient description of a genus…requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can “visualize or recognize” the members of the genus”. 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 95.4% identical to the polypeptide of amino acids 3-433 of SEQ ID NO: 35. Applicants cite Table 8, p. 224,-251, to describe modified polypeptides.
Applicant's arguments filed October 7, 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 17 amino acid residues of amino acids 3-433 of SEQ ID NO: 35 are substituted. The location of the possible modifications and the type of modifications are not described for the genus claimed, though some locations where substitutions cannot be made are claimed. The tables cited refer to single amino acid mutation/substitutions in the parent PH20 hyaluronidase. The modified polypeptide with multiple 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 44-66 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 or some undisclosed polypeptide activity, does not reasonably provide enablement for the genus of any modified polypeptide comprising any 17 amino substitutions within amino acids 3-433 of SEQ ID NO: 35 as currently claimed, wherein none of the substitutions are present at any of residues 25, 107-137, 170-200, 203, 242-262, 316, 333, 341, 346, 352, 358, 400, 402, 408, 423, and 429 with reference to SEQ ID NO: 35. The claims do not provide enablement for any PH20 hyaluronidase activity that degrades hyaluronan or some undisclosed polypeptide activity, wherein none of the substitutions are present at any of residues 25, 107-137, 170-200, 203, 242-262, 316, 333, 341, 346, 352, 358, 400, 402, 408, 423, and 429 with reference to SEQ ID NO: 35. 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. It appears the polypeptide of SEQ ID NO: 6 is a PH20 hyaluronidase. 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.
In In re Wands, 8 USPQ2d 1400 (Fed. Cir., 1988) eight factors should be addressed in determining enablement.
While the analysis and conclusion of a lack of enablement are based on the factors discussed in MPEP § 2164.01(a) and the evidence as a whole, it is not necessary to discuss each factor in the written enablement rejection. The language should focus on those factors, reasons, and evidence that lead the examiner to conclude that the specification fails to teach how to make and use the claimed invention without undue experimentation, or that the scope of any enablement provided to one skilled in the art is not commensurate with the scope of protection sought by the claims. This can be done by making specific findings of fact, supported by the evidence, and then drawing conclusions based on these findings of fact. For example, doubt may arise about enablement because information is missing about one or more essential parts or relationships between parts which one skilled in the art could not develop without undue experimentation. In such a case, the examiner should specifically identify what information is missing and why one skilled in the art could not supply the information without undue experimentation. See MPEP § 2164.06(a). References should be supplied if possible to support a prima facie case of lack of enablement, but are not always required. In re Marzocchi, 439 F.2d 220, 224, 169 USPQ 367, 370 (CCPA 1971). However, specific technical reasons are always required.
1) The nature of the invention: the instant claims are directed to a modified polypeptide consisting of amino acids 3-433 of SEQ ID NO: 35, wherein the modified polypeptide has 17 amino acid substitutions with reference to amino acids 3-433 of SEQ ID NO: 35, and wherein none of the substitutions are present at any of residues 25, 107-137, 170-200, 203, 242-262, 316, 333, 341, 346, 352, 358, 400, 402, 408, 423, and 429 with reference to SEQ ID NO: 35. The claims are drawn to a modified polypeptide, wherein at least one of the 17 amino acid substitutions is with an amino acid selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, methionine and proline. The claims are drawn to a modified polypeptide, wherein at least one of the 17 amino acid substitutions is with an amino acid selected from the group consisting of serine, threonine, cysteine, asparagine, and glutamine. The claims are drawn to a modified polypeptide, wherein at least one of the 17 amino acid substitutions is with an amino acid selected from the group consisting of phenylalanine and tryptophan. The claims are drawn to a modified polypeptide, wherein at least one of the 17 amino acid substitutions is with an amino acid selected from tyrosine. The claims are drawn to a modified polypeptide, wherein at least one of the 17 amino acid substitutions is with an amino acid selected from the group consisting of aspartic acid, glutamic acid, lysine, arginine, and histidine. The claims are drawn to a modified polypeptide, wherein at least one of the 17 amino acid substitutions is substation of alanine with glycine or serine. The claims are drawn to a modified polypeptide, wherein at least one of the 17 amino acid substitutions is substitution of arginine with lysine. The claims are drawn to a modified polypeptide, wherein at least one of the 17 amino acid substitutions is substitution of asparagine with glutamine or histidine. The claims are drawn to a modified polypeptide, wherein at least one of the 17 amino acid substitutions is substitution of cysteine with serine. The claims are drawn to a modified polypeptide, wherein at least one of the 17 amino acid substitutions is substitution of glutamine with asparagine. The claims are drawn to a modified polypeptide, wherein at least one of the 17 amino acid substitutions is substitution of glutamic acid with aspartic acid. The claims are drawn to a modified polypeptide, wherein at least one of the 17 amino acid substitutions is substitution of glycine with alanine or proline. The claims are drawn to a modified polypeptide, wherein at least one of the 17 amino acid substitutions is substitution of histidine with asparagine or glutamine. The claims are drawn to a modified polypeptide, wherein at least one of the 17 amino acid substitutions is substitution of isoleucine with leucine or valine. The claims are drawn to a modified polypeptide, wherein at least one of the 17 amino acid substitutions is substitution of leucine with isoleucine or valine. The claims are drawn to a modified polypeptide, wherein at least one of the 17 amino acid substitutions is substitution of lysine with arginine, glutamine, or tyrosine. The claims are drawn to a modified polypeptide, wherein at least one of the 17 amino acid substitutions is substitution of methionine with leucine, tyrosine, or isoleucine. The claims are drawn to a modified polypeptide, wherein at least one of the 17 amino acid substitutions is substitution of phenylalanine with methionine, leucine, or tyrosine. The claims are drawn to a modified polypeptide, wherein at least one of the 17 amino acid substitutions is substitution of serine with threonine. The claims are drawn to a modified polypeptide, wherein at least one of the 17 amino acid substitutions is substitution of threonine with serine. The claims are drawn to a modified polypeptide, wherein at least one of the 17 amino acid substitutions is substitution of tryptophan with tyrosine. The claims are drawn to a modified polypeptide, wherein at least one of the 17 amino acid substitutions is substitution of tyrosine with tryptophan or phenylalanine. The claims are drawn to a modified polypeptide, wherein at least one of the 17 amino acid substitutions is substitution of valine with isoleucine or leucine.
3) The predictability or unpredictability of the art: & 6) The quantity of experimentation necessary: & 7.) The state of the prior art: 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) ; previously cited) 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.
4) The amount of direction or guidance presented: & 5) 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 specification does not provide direction as to which modified polypeptides will result in modified hyaluronidase enzymes with other functional ability, including the ability to confer contraception. There is undue amount of experimentation, with a lack of direction as to what modified polypeptides will be used to confer contraception as potentially implicated for a specific use of the modified polypeptide.
8.) Level of skill in the art: the level of skill in this art is high, at least that of a doctoral scientist with several years of experience in the art.
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 44-66 are rejected under 35 U.S.C. 101 because the claimed invention lacks patentable utility. Claims 24 and 44-66 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: 35 is a PH20 hyaluronidase, but is not claimed to have any activity or specific and substantial utility.
Claims 24 and 44-66 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.
/ANAND U DESAI/Primary Examiner, Art Unit 1656