DETAILED CORRESPONDENCE
Status of the Application
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on December 23, 2025 has been entered.
The present application is being examined under the pre-AIA first to invent provisions.
Claims 32-39, 41-43, and 45-65 are pending in the application.
Applicant’s amendments to the claims, filed December 23, 2025, March 12, 2026, April 24, 2026, and May 11, 2026, are acknowledged. Applicant’s amendment filed May 11, 2026 has been entered and replaces all prior versions and listings of the claims.
Claims 24, 40, and 44 are canceled in applicant’s amendment filed May 11, 2026 and rejections previously applied to these claims are withdrawn.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election/Restrictions
Applicant's election with traverse of the species of amino acid positions 104, 105, 201, 344, 348, and 355 for amino acid replacement in the reply filed May 11, 2026 is acknowledged. The traversal is on the ground that the genus of the polypeptides in claim 55 is defined by amino acid replacements at specific positions relative to the single amino acid sequence of amino acids 38-468 of SEQ ID NO: 6, and examination of the genus would not be unduly burdensome because the genus of polypeptides is directed to variations within a single sequence framework.
This is not found persuasive because each species is a different position or group of positions for amino acid replacement and at least a separate text-based search is required for each of the species. As such, contrary to applicant’s position, there is a serious search and examination burden for the patentably distinct species.
The requirement is still deemed proper and is therefore made FINAL.
Claims 37-39, 41-43, 46, 47, 49, and 51-53 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected species, there being no allowable generic or linking claim.
Claims 32-36, 45, 48, 50, and 54-65 are being examined on the merits with claims 45, 48, 50, 54, and 55 being examined only to the extent the claims read on the elected subject matter.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on December 23, 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS has been considered by the examiner.
Specification/Informalities
The specification is objected to because the sequence listing incorporation statement at p. 5, lines 10-14 of the substitute specification filed September 30, 2025 does not comply with the requirements for a sequence listing, which require the size of the XML file to be listed in bytes (not kilobytes). See MPEP 2422.03. and see MPEP 2422.03(a) for additional information pertaining to EFS-Web submission of sequence listings.
Drawings
The drawings filed March 5, 2025 and September 30, 2025 are objected to because Figures 1 and 2 display sequences that are included in the Sequence Listing XML, e.g., Figure 1 displays SEQ ID NO: 7. Pursuant to 37 CFR 1.83(a), sequences that are included in the "Sequence Listing XML" should not be duplicated in the drawings (see MPEP 2412.06).
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 63-65 are objected to for reciting “wherein the polypeptide consists of … amino acid replacements” and in the interest of improving claim form, it is suggested that the noted phrase be amended to recite (with markings to show changes made) “wherein the polypeptide consists of … amino acid replacements with reference to amino acids 38-468 of SEQ ID NO: 6”.
Claim Rejections - 35 USC § 112(b)
Claims 32-36, 45, 48, 50, and 54-65 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 55 (claims 32-36, 45, 48, 50, 54, and 56-65 dependent therefrom) is confusing in the recitation of “polypeptide comprising amino acids 38-468 of SEQ ID NO: 6” and “the polypeptide comprises an amino acid replacement…located at amino acid position…with reference to amino acids 38-468 of SEQ ID NO: 6.” It is unclear as to how the claimed polypeptide can simultaneously comprise amino acids 38-468 of SEQ ID NO: 6 and comprise an amino acid replacement of the recited position(s) of amino acids 38-468 of SEQ ID NO: 6. It is suggested that applicant clarify the meaning of the claim.
Claims 59 and 62 depend from claim 55 and thus, claims 59 and 62 incorporate all limitations of claim 55, which recites (in relevant part) “the polypeptide…has a hyaluronidase activity that is at least 40% of a hyaluronidase activity with respect to a reference polypeptide consisting of amino acids 38-468 of SEQ ID NO: 6.” Claims 59 and 62 are entirely unclear in requiring the claimed polypeptide to have a hyaluronidase activity that is at least 40% of a hyaluronidase activity with respect to a reference polypeptide consisting of amino acids 38-468 of SEQ ID NO: 6, and also requiring an additional amino acid replacement located at an amino acid position that confers less than 40% hyaluronidase activity when the amino acid position that confers less than 40% hyaluronidase activity is replaced alone in a polypeptide consisting of amino acids 38-468 of SEQ ID NO: 6 and the amino acid replacement. It is suggested that applicant clarify the meanings of the claims.
Claim Interpretation
Claim 55 (claims 56-60 dependent therefrom) is drawn to (in relevant part) a polypeptide comprising amino acids 38-468 of SEQ ID NO: 6, wherein
(i) the polypeptide does not comprise amino acids 1-37 of SEQ ID NO: 6 and amino acids 469-509 of SEQ ID NO: 6 and
(ii) the polypeptide comprises an amino acid replacement, wherein the polypeptide comprising the amino acid replacement has a hyaluronidase activity that is at least 40% of a hyaluronidase activity with respect to a reference polypeptide consisting of amino acids 38-468 of SEQ ID NO: 6, and wherein the amino acid replacement is located at amino acid positions 104, 105, 201, 344, 348, and 355 with reference to amino acids 38-468 of SEQ ID NO: 6.
Claim 55 does not specify the replacement amino acids at positions 104, 105, 201, 344, 348, and 355 corresponding to amino acids 38-468 of SEQ ID NO: 6. Given a broadest reasonable interpretation, the replacement amino acids at positions 104, 105, 201, 344, 348, and 355 corresponding to amino acids 38-468 of SEQ ID NO: 6 are unlimited and encompass at least any one of the 19 other common amino acids.
Outside of the replacement amino acids at positions 104, 105, 201, 344, 348, and 355 corresponding to amino acids 38-468 of SEQ ID NO: 6, claim 55 does not limit the remaining amino acid sequence of the claimed polypeptide. Given a broadest reasonable interpretation, other than the replacement amino acids at positions 104, 105, 201, 344, 348, and 355 corresponding to amino acids 38-468 of SEQ ID NO: 6, the remaining amino acid sequence of the claimed polypeptide encompasses any amino acid modifications (i.e., amino acid substitutions, deletions, insertions, and additions) to any amino acids other than positions 104, 105, 201, 344, 348, and 355 relative to amino acids 38-468 of SEQ ID NO: 6.
Claims 32-36, 45, 48, 50, and 54 limit the replacement amino acids at positions 104, 105, 201, 344, 348, and 355 to a specific amino acid or specific amino acids. Other than the replacement amino acids at positions 104, 105, 201, 344, 348, and 355 corresponding to amino acids 38-468 of SEQ ID NO: 6, the remaining sequence of the claimed polypeptide encompasses any amino acid modifications (i.e., amino acid substitutions, deletions, insertions, and additions) relative to amino acids 38-468 of SEQ ID NO: 6.
Claims 59 and 62 are drawn to the polypeptide of claims 58 and 60, respectively, wherein the additional amino acid replacement is located at an amino acid position that confers less than 40% hyaluronidase activity when the amino acid position that confers less than 40% hyaluronidase activity is replaced alone in a polypeptide consisting of amino acids 38-468 of SEQ ID NO: 6 and the amino acid replacement.
As such, the polypeptide of claims 59 and 62 has a hyaluronidase activity that is at least 40% of a hyaluronidase activity with respect to a reference polypeptide consisting of amino acids 38-468 of SEQ ID NO: 6, and comprises an additional amino acid replacement is located at an amino acid position that confers less than 40% hyaluronidase activity when the amino acid position that confers less than 40% hyaluronidase activity is replaced alone in a polypeptide consisting of amino acids 38-468 of SEQ ID NO: 6 and the amino acid replacement.
Claim 61 is drawn to the polypeptide of claim 60, wherein the additional amino acid replacement is not located at amino acid position 38, 40, 43, 44, 46, 47, 49, 50, 55, 57, 58, 59, 61, 62, 63, 70, 71, 72, 74, 76, 77, 78, 80, 81, 82, 83, 84, 85, 86, 87, 89, 93, 95, 96, 98, 102, 104, 105, 106, 107, 108, 109, 110, 112, 114, 115, 116, 117, 118, 119, 120, 121, 126, 128, 129, 131, 132, 133, 134, 137, 140, 141, 173, 176, 177, 178, 180, 181, 182, 184, 185, 187, 188, 189, 191, 192, 193, 194, 195, 196, 197, 199, 200, 201, 202, 204, 241, 243, 244, 250, 251, 252, 254, 255, 256, 257, 259, 265, 266, 267, 269, 270, 272, 273, 274, 275, 298, 300, 301, 302, 304, 305, 306, 307, 308, 309, 311, 313, 315, 322, 323, 325, 326, 329, 332, 333, 335, 336, 337, 338, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 352, 353, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 366, 370, 373, 374, 377, 378, 383, 386, 388, 391, 394, 395, 404, 408, 411, 413, 416, 418, 420, 422, 423, 426, 428, 429, 430, 431, 432, 433, 434, 438, 439, 440, 441, 444, 445, 447, 449, 450, 454, 455, 457, 460, 463, 467, or 468 with reference to amino acids 38-468 of SEQ ID NO: 6.
Other than excluding an additional amino acid replacement at the recited amino acid position corresponding to amino acids 38-468 of SEQ ID NO: 6, the remaining sequence of the claimed polypeptide encompasses any amino acid modifications (i.e., amino acid substitutions, deletions, insertions, and additions) relative to amino acids 38-468 of SEQ ID NO: 6.
Claims 63-65 are drawn to the polypeptide of claim 60, wherein the polypeptide consists of 5 amino acid replacements, 10 amino acid replacements, and 15 amino acid replacements, respectively.
Claims 63-65 depend from claims 55 and 60 and thus incorporate all limitations of claims 55 and 60. The use of "consists" in the phrase “consists of…amino acid replacements” in claims 63-65 does not limit the open-ended "comprising" language in the phrase “the polypeptide comprises an amino acid replacement” in claim 55 and the phrase “polypeptide further comprises an additional amino acid replacement” in claim 60 (see MPEP 2111.03.II). As such, other than the replacement amino acids at positions 104, 105, 201, 344, 348, and 355 corresponding to amino acids 38-468 of SEQ ID NO: 6, the remaining sequence of the claimed polypeptide encompasses any amino acid modifications (i.e., amino acid substitutions, deletions, insertions, and additions) relative to amino acids 38-468 of SEQ ID NO: 6.
Claim Rejections - 35 USC § 112(a)
Claims 32-36, 45, 48, 50, and 54-65 are rejected under 35 U.S.C. 112(a) 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 at the time the application was filed, had possession of the claimed invention.
MPEP 2163.II.A.2.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163 states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
MPEP § 2163 further states that “[s]atisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus…Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’ Such correlations may be established ‘by the inventor as described in the specification,’ or they may be ‘known in the art at the time of the filing date.’"
The factors considered in the Written Description requirement are (1) level of skill and knowledge in the art, (2) partial structure, (3) physical and/or chemical properties, (4) functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the (5) method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient." MPEP § 2163.
The claims have been interpreted as described in detail above. Given the substantial structural variation among the members of the genus of claimed polypeptides, the genus is considered to encompass species with widely variant amino acid sequences.
The specification discloses the actual reduction to practice of single amino acid variants of most of the amino acids of the sequence of amino acids 38-468 of SEQ ID NO: 6 that maintain at least 40% of the hyaluronidase activity of the PH20 polypeptide of SEQ ID NO: 3 (see Table 3 beginning at p. 111 of the substitute specification filed September 30, 2025). The specification fails to disclose even a single representative species of the a polypeptide comprising the elected combination of amino acid replacements at amino acid positions 104, 105, 201, 344, 348, and 355 that has a hyaluronidase activity that is at least 40% of a hyaluronidase activity with respect to a reference polypeptide consisting of amino acids 38-468 of SEQ ID NO: 6.
Regarding the level of skill and knowledge in the art of amino acid modification, MPEP 2144.08.II.A.4.(c) states, "[i]n the area of biotechnology, an exemplified species may differ from a claimed species by a conservative substitution ("the replacement in a protein of one amino acid by another, chemically similar, amino acid... [which] is generally expected to lead to either no change or only a small change in the properties of the protein." Dictionary of Biochemistry and Molecular Biology 97 (John Wiley & Sons, 2d ed. 1989)). The effect of a conservative substitution on protein function depends on the nature of the substitution and its location in the chain. Although at some locations a conservative substitution may be benign, in some proteins only one amino acid is allowed at a given position. For example, the gain or loss of even one methyl group can destabilize the structure if close packing is required in the interior of domains. James Darnell et al., Molecular Cell Biology 51 (2d ed. 1990)."
The reference of Singh et al. (Curr. Protein Pept. Sci. 18:1-11, 2017; cited on the attached Form PTO-892) reviews various protein engineering methods and discloses that despite the availability of an ever-growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes (see p. 7, column 1, top).
The unpredictability associated with amino acid substitution is exemplified by the reference of Zhang et al. (Structure 26:1474-1485, 2018; cited on the attached Form PTO-892), which discloses that even a substitution of a surface residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide (p. 1475, column 1).
More specific to the claimed invention, the reference of Zhang et al. (J. Biol. Chem. 284:9433-9442, 2009; cited on the attached Form PTO-892) teaches that based on homologous sequences, Asp129 was predicted to be an essential catalytic residue and would be critical for catalytic activity of human hyaluronidase 1 (p. 9436, column 2, top and p. 9437, column 2, middle), however, Asp129 was empirically determined to be non-essential because significant activity of an Asp129Asn substitution mutant was retained (p. 9437, column 2, middle).
Given that the claimed genus of polypeptides encompasses species having widely variant structures while the specification discloses only a relative few representative species of single amino acid substitutions at each of positions 104, 105, 201, 344, 348, and 355 with reference to amino acids 38-468 of SEQ ID NO: 6 and the specification fails to disclose even a single representative species of the claimed polypeptide with amino acid substitutions at each of positions 104, 105, 201, 344, 348, and 355, and given that there was a very high level of unpredictability in the art of amino acid modification at the time of the invention, the specification is considered to be insufficient to describe the claimed genus of polypeptides. In this case, the specification at best describes a research plan for making, testing, and identifying those species that are encompassed by the claimed genus of polypeptides, however, a plan for making the claimed invention is not sufficient to show possession at the time of filing. One of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus, and thus, that the applicant was not in possession of the recited genus.
For these reasons, it is the examiner’s position that the specification fails to adequately describe the claimed invention.
RESPONSE TO REMARKS: In summary, applicant argues in the response filed December 23, 2025 that in view of the recited structural and functional features of the independent claim, one of skill in the art would recognize that applicant was in possession of the claimed invention.
Applicant’s arguments are not found persuasive. For the reasons set forth above, particularly that the claimed genus of polypeptides encompasses species having widely variant structures, the specification fails to disclose even a single representative species of the claimed polypeptide with amino acid substitutions at each of positions 104, 105, 201, 344, 348, and 355, and there was a very high level of unpredictability in the art of amino acid modification at the time of the invention, one of skill in the art would reasonably conclude that applicant was not in possession of the claimed genus of polypeptides.
Claims 32-36, 45, 48, 50, and 54-65 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for any one of the “Active Mutants” as disclosed at Table 3 beginning at p. 111 of the substitute specification filed September 30, 2025, does not reasonably provide enablement for all polypeptides as broadly encompassed by the claims. 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/or use the invention commensurate in scope with these claims.
“The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue.” In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976). Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)) as follows: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01(a). The Factors considered to be most relevant to the instant rejection are addressed in detail below.
The nature of the invention: According to the instant specification, many therapeutic hyaluronidases can be immunogenic for treatment of humans and improved hyaluronan-degrading enzymes, such as hyaluronidases, and compositions thereof that can be used for treatment are needed (paragraph bridging pp. 5-6) and provided are modified PH20 polypeptides that have an altered property or properties compared to the PH20 polypeptide that do not have the modification(s) (p. 6, first full paragraph).
The breadth of the claims: The claims have been interpreted as described in detail above.
The state of the prior art; The level of one of ordinary skill; and The level of predictability in the art: According to MPEP 2164.03, “…what is known in the art provides evidence as to the question of predictability.” “[I]f one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art.” See MPEP § 2164.03.
Regarding the level of skill and knowledge in the art of amino acid modification, MPEP 2144.08.II.A.4.(c) states, "[i]n the area of biotechnology, an exemplified species may differ from a claimed species by a conservative substitution ("the replacement in a protein of one amino acid by another, chemically similar, amino acid... [which] is generally expected to lead to either no change or only a small change in the properties of the protein." Dictionary of Biochemistry and Molecular Biology 97 (John Wiley & Sons, 2d ed. 1989)). The effect of a conservative substitution on protein function depends on the nature of the substitution and its location in the chain. Although at some locations a conservative substitution may be benign, in some proteins only one amino acid is allowed at a given position. For example, the gain or loss of even one methyl group can destabilize the structure if close packing is required in the interior of domains. James Darnell et al., Molecular Cell Biology 51 (2d ed. 1990)."
The reference of Singh et al. (Curr. Protein Pept. Sci. 18:1-11, 2017; cited on the attached Form PTO-892) reviews various protein engineering methods and discloses that despite the availability of an ever-growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes (see p. 7, column 1, top).
The unpredictability associated with amino acid substitution is exemplified by the reference of Zhang et al. (Structure 26:1474-1485, 2018; cited on the attached Form PTO-892), which discloses that even a substitution of a surface residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide (p. 1475, column 1).
More specific to the claimed invention, the reference of Zhang et al. (J. Biol. Chem. 284:9433-9442, 2009; cited on the attached Form PTO-892) teaches that based on homologous sequences, Asp129 was predicted to be an essential catalytic residue and would be critical for catalytic activity of human hyaluronidase 1 (p. 9436, column 2, top and p. 9437, column 2, middle), however, Asp129 was empirically determined to be non-essential because significant activity of an Asp129Asn substitution mutant was retained (p. 9437, column 2, middle).
Based on the evidence of record, one of skill in the art would recognize a high level of unpredictability in the art of amino acid modification.
The amount of direction provided by the inventor and The existence of working examples: The specification discloses the working examples of single amino acid variants of most of the amino acids of the sequence of amino acids 38-468 of SEQ ID NO: 6 that maintain at least 40% of the hyaluronidase activity of the PH20 polypeptide of SEQ ID NO: 3 (see Table 3 beginning at p. 111 of the substitute specification filed September 30, 2025). The specification fails to disclose even a single working example of a polypeptide comprising the elected combination of amino acid replacements at amino acid positions 104, 105, 201, 344, 348, and 355 that has a hyaluronidase activity that is at least 40% of a hyaluronidase activity with respect to a reference polypeptide consisting of amino acids 38-468 of SEQ ID NO: 6.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure: In the Federal Circuit decision of Idenix Pharmaceuticals LLC v. Gilead Sciences Inc., 941 F.3d 1149, 1156 (Fed. Cir. 2019), the court stated that “the key enablement question is whether a person of ordinary skill in the art would know, without undue experimentation, which [species] would be effective….because of the many thousands of [species] which need to be screened for…efficacy, the quantity of experimentation needed is large and weighs in favor of non-enablement.” While methods for modifying the amino acid sequence of a polypeptide were known before the effective filing date, it was not routine in the art to screen by a trial and error process for a vast number of polypeptides having a hyaluronidase activity that is at least 40% of a hyaluronidase activity with respect to a reference polypeptide consisting of amino acids 38-468 of SEQ ID NO: 6 as broadly encompassed by the claims.
In view of the broad scope of the claimed genus, the lack of guidance and working examples provided in the specification, and the high degree of unpredictability as evidenced by the prior art, undue experimentation would be necessary for a skilled artisan to make and use the entire scope of the claimed invention. Applicants have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
RESPONSE TO REMARKS: In summary, applicant argues in the response filed December 23, 2025 that in view of the recited structural and functional features of the independent claim and in view of the Factors of In re Wands, only routine experimentation would have been required for one of skill in the art to make and use the full scope of the claimed invention.
Applicant’s arguments are not found persuasive. For the reasons set forth above in the detailed analysis of the Factors of In re Wands, particularly the broad scope of polypeptides encompassed by the claims, the absence of even a single working example of the claimed polypeptide with amino acid substitutions at each of positions 104, 105, 201, 344, 348, and 355, the very high level of unpredictability in the art of amino acid modification at the time of the invention, and the quantity of experimentation required to make all polypeptides encompassed by the claims, undue experimentation would have been required to make and use the full scope of the claimed invention.
Claims 45, 48, 50, 54, 56-65 are rejected under 35 U.S.C. 112(a) 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 at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
MPEP § 2163.II.A.3.(b) states, “when filing an amendment an applicant should show support in the original disclosure for new or amended claims”. See also MPEP 714.02. MPEP § 2163.II.A.3.(b) further states, “[i]f the originally filed disclosure does not provide support for each claim limitation, or if an element which applicant describes as essential or critical is not claimed, a new or amended claim must be rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112, para. 1, as lacking adequate written description”. According to MPEP § 2163.I.B, “While there is no in haec verba requirement, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure” and “The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117”.
Claims 45, 48, 50, 54, 56, and 57 (claims 58-65 dependent therefrom) recite specific combinations of amino acid replacements. Applicant fails to show support for the specific combinations of amino acid replacements as recited in claims 45, 48, 50, 54, 56, and 57. While the original application discloses single amino acid variants of most of the amino acids of the sequence of amino acids 38-468 of SEQ ID NO: 6 that maintain at least 40% of the hyaluronidase activity of the PH20 polypeptide of SEQ ID NO: 3 (see Table 3 beginning at p. 111 of the substitute specification filed September 30, 2025) and generically discloses “combinations of modifications” (e.g., substitute specification filed September 30, 2025 at p. 9, lines 24-26) and “one or more amino acid replacements” (e.g., substitute specification filed September 30, 2025 at p. 6, lines 12-14), there is no apparent descriptive support for the specific combinations recited in claims 45, 48, 50, 54, 56, and 57 in the original application as filed. In the absence of descriptive support, the recitation of these specific combinations is considered to introduce new matter into the claims.
Claim Rejections - 35 USC § 101
The rejection of claims 32-43 and 45-54 under 35 U.S.C. 101 because the claimed invention lacks patentable utility is withdrawn in view of applicant’s amendment to the claims and upon further consideration of the rejection.
Claim Rejections - Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Co-Pending Application No. 19/071,005
Claims 32-36, 45, 48, 50, and 54-65 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 44-48, 57, 60, 62, 66-68, and 71-75 of co-pending application no. 19/071,005 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other for reasons that follow.
Regarding instant claims 55-58, 60, and 61, claim 67 of the reference application recites a polypeptide comprising amino acids 3-433 of SEQ ID NO: 35, wherein the polypeptide (i) does not comprise amino acids 1-37 of SEQ ID NO: 6 and amino acids 469-509 of SEQ ID NO: 6, and (ii) comprises at least one amino acid replacement, wherein the polypeptide comprising the amino acid replacement has a hyaluronidase activity that is at least 40% of a hyaluronidase activity with respect to a reference polypeptide consisting of amino acids 3-43 of SEQ ID NO: 35, and wherein the amino acid replacement is located at amino acid position 3, 5, 8, 9, 11, 12, 14, 15, 16, 17, 18, 19, 20, 22, 23, 24, 26, 27, 28, 35, 36, 37, 39, 41, 42, 43, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 58, 60, 61, 62, 63, 64, 67, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 81, 82, 83, 84, 85, 86, 91, 93, 94, 96, 97, 98, 99, 100, 102, 105, 106, 138, 141, 142, 143, 145, 146, 147, 149, 150, 152, 153, 154, 156, 157, 158, 159, 160, 161, 162, 164, 165, 166, 167, 169, 201, 206, 208, 209, 210, 215, 216, 217, 219, 220, 221, 222, 223, 224, 225, 227, 228, 229, 230, 231, 232, 234, 235, 237, 238, 239, 240, 241, 263, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 276, 278, 279, 280, 281, 287, 288, 290, 291, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 317, 318, 319, 320, 321, 323, 324, 325, 326, 327, 328, 330, 331, 332, 335, 336, 337, 338, 339, 342, 343, 344, 345, 348, 350, 351, 353, 354, 355, 356, 359, 360, 362, 363, 366, 369, 370, 372, 373, 376, 379, 381, 382, 383, 385, 387, 388, 391, 393, 394, 395, 396, 397, 398, 399, 403, 404, 405, 406, 409, 410, 412, 414, 415, 419, 420, 422, 425, 428, 430, 432, and 433, or any combination thereof, with reference to amino acids 3-433 of SEQ ID NO: 35;
claim 68 of the reference application recites the polypeptide of claim 67, wherein the amino acid replacement is located at amino acid positions 309, 313, and 320 with reference to amino acids 3-433 of SEQ ID NO: 35; and
claim 74 of the reference application recites the polypeptide of claim 69, wherein the additional amino acid replacement is located at amino acid positions 69, 70, and 166 with reference to amino acids 3-433 of SEQ ID NO: 35.
The sequence of amino acids 3-433 of SEQ ID NO: 3 of the reference application is identical to the sequence of amino acids 38-468 of instant SEQ ID NO: 6 and amino acid positions 69, 70, 166, 309, 313, and 320 of amino acids 3-433 of SEQ ID NO: 3 of the reference application correspond to amino acid positions 104, 105, 201, 344, 348, and 355, respectively, of amino acids 38-468 of SEQ ID NO: 6.
Regarding instant claim 32, claim 44 of the reference application recites the polypeptide of claim 55, wherein the amino acid replacement is an amino acid selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, methionine and proline.
Regarding instant claim 33, claim 45 of the reference application recites the polypeptide of claim 55, wherein the amino acid replacement is an amino acid selected from the group consisting of serine, threonine, cysteine, asparagine and glutamine.
Regarding instant claim 34, claim 46 of the reference application recites the polypeptide of claim 55, wherein the amino acid replacement is an amino acid selected from the group consisting of phenylalanine and tryptophan.
Regarding instant claim 35, claim 47 of the reference application recites the polypeptide of claim 55, wherein the amino acid replacement is with an amino acid selected from tyrosine.
Regarding instant claim 36, claim 48 of the reference application recites the polypeptide of claim 55, wherein the amino acid replacement is an amino acid selected from the group consisting of aspartic acid, glutamic acid, lysine, arginine and histidine.
Regarding instant claim 45, claim 57 of the reference application recites the polypeptide of claim 55, wherein the amino acid amino acid replacement is a substitution of isoleucine with located at amino acid position 9, 41, 46, 67, 70, 79, 83, 96, 169, 208, 271, 301, 303, 309, 326, 331, 353, or a combination thereof is leucine or valine.
Regarding instant claim 48, claim 60 of the reference application recites the polypeptide of claim 55, wherein the amino acid replacement is a substitution of methionine with located at amino acid position 35, 310, 313, 323, or a combination thereof is leucine, tyrosine or isoleucine.
Regarding instant claim 50, claim 62 of the reference application recites the polypeptide of claim 55, wherein the amino acid replacement is a substitution of serine with located at amino acid position 22, 36, 39, 43, 69, 84, 145, 215, 221, 235, 308, 312, 315, 342, 359, 360, 395, 404, or a combination thereof is threonine.
Regarding instant claim 54, claim 66 of the reference application recites the polypeptide of claim 55, wherein the amino acid replacement is a substitution of valine with located at amino acid position 8, 12, 58, 73, 75, 102, 142, 166, 206, 237, 265, 272, 287, 294, 302, 351, 414, 420, 422, 428, or a combination thereof is isoleucine or leucine.
Regarding instant claims 59 and 62, claim 75 of the reference application recites the polypeptide of claim 74, wherein the additional amino acid replacement is located at an amino acid position that confers less than 40% hyaluronidase activity when the amino acid position that confers less than 40% hyaluronidase activity is replaced alone in a polypeptide consisting of amino acids 3-433 of SEQ ID NO: 35 and the additional amino acid replacement.
Regarding instant claims 63-65, claims 71-73 of the reference application recite the polypeptide of claim 70, wherein the polypeptide consists of 5, 10, or 15 amino acid replacements, respectively.
Therefore, the claims of this application are unpatentable over the claims of the reference application. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Co-Pending Application No. 19/071,055
Claims 32-36, 45, 48, 50, and 54-65 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 32-36, 45, 48, 50, 55-63, and 66 of co-pending application no. 19/071,055 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other for reasons that follow.
Regarding instant claims 55-58 and 60, claim 55 of the reference application recites a polypeptide comprising amino acids 38-468 of SEQ ID NO: 6, wherein
(i) the polypeptide does not comprise amino acids 1-37 of SEQ ID NO: 6 and amino acids 469-509 of SEQ ID NO: 6 and
(ii) the polypeptide comprises an amino acid replacement, wherein the polypeptide comprising the amino acid replacement has a hyaluronidase activity that is at least 40% of a hyaluronidase activity with respect to a reference polypeptide consisting of amino acids 38-468 of SEQ ID NO: 6, and wherein the amino acid replacement is located at amino acid position 38, 40, 43, 44, 46, 47, 49, 50, 55, 57, 58, 59, 61, 62, 63, 70, 71, 72, 74, 76, 77, 78, 80, 81,82,83,84,85,86,87,89,93,95,96,98, 102,104, 105, 106, 107, 108, 109, 110, 112, 114, 115, 116, 117, 118, 119, 120, 121, 126, 128, 129, 131, 132, 133, 134, 137, 140, 141, 173, 176, 177, 178, 180, 181, 182, 184, 185, 187, 188, 189, 191, 192, 193, 194, 195, 196, 197, 199, 200, 201, 202, 204, 241, 243, 244, 250, 251, 252, 254, 255, 256, 257, 259, 265, 266, 267, 269, 270, 272, 273, 274, 275, 298, 300, 301, 302, 304, 305, 306, 307, 308, 309, 311, 313, 315, 322, 323, 325, 326, 329, 332, 333, 335, 336, 337, 338, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 352, 353, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 366, or any combination thereof, with reference to amino acids 38-468 of SEQ ID NO: 6;
claim 56 of the reference application recites the polypeptide of claim 55, wherein the amino acid replacement is located at amino acid positions 344, 348, and 355 with reference to amino acids 38-468 of SEQ ID NO: 6;
claim 57 of the reference application recites the polypeptide of claim 56, wherein the polypeptide further comprises an additional amino acid replacement; and
claim 62 of the reference application recites the polypeptide of claim 57, wherein the additional amino acid replacement is located at amino acid position 104, 105, and 201 with reference to amino acids 38-468 of SEQ ID NO: 6.
The sequence of amino acids 38-468 of SEQ ID NO: 6 of the reference application is identical to the sequence of amino acids 38-468 of instant SEQ ID NO: 6.
Regarding instant claim 32, claim 32 of the reference application recites the polypeptide of claim 55, wherein the amino acid replacement is an amino acid selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, methionine and proline.
Regarding instant claim 33, claim 33 of the reference application recites the polypeptide of claim 55, wherein the amino acid replacement is an amino acid selected from the group consisting of serine, threonine, cysteine, asparagine and glutamine.
Regarding instant claim 34, claim 34 of the reference application recites the polypeptide of claim 55, wherein the amino acid replacement is an amino acid selected from the group consisting of phenylalanine and tryptophan.
Regarding instant claim 35, claim 35 of the reference application recites the polypeptide of claim 55, wherein the amino acid replacement is with an amino acid selected from tyrosine.
Regarding instant claim 36, claim 36 of the reference application recites the polypeptide of claim 55, wherein the amino acid replacement is an amino acid selected from the group consisting of aspartic acid, glutamic acid, lysine, arginine and histidine.
Regarding instant claim 45, claim 45 of the reference application recites the polypeptide of claim 55, wherein the amino acid amino acid replacement is a substitution of isoleucine with located at amino acid position 44, 76, 81, 102, 105, 114, 118, 131, 204, 243, 306, 336, 338, 344, 361, 366, or a combination thereof is leucine or valine.
Regarding instant claim 48, claim 48 of the reference application recites the polypeptide of claim 55, wherein the amino acid replacement is a substitution of methionine with located at amino acid position 70, 345, 348, 358, or a combination thereof is leucine, tyrosine or isoleucine.
Regarding instant claim 50, claim 50 of the reference application recites the polypeptide of claim 55, wherein the amino acid replacement is a substitution of serine with located at amino acid position 57, 71, 74, 78, 104, 119, 180, 250, 256, 270, 343, 347, 350, or a combination thereof is threonine.
Regarding instant claim 54, claim 54 of the reference application recites the polypeptide of claim 55, wherein the amino acid replacement is a substitution of valine with located at amino acid position 43, 47, 93, 108, 110, 137, 177, 201, 241, 272, 300, 307, 322, 329, 337, or a combination thereof is isoleucine or leucine.
Regarding instant claims 59 and 62, claims 58 and 63 of the reference application recite the polypeptide of claim 57 or 62, respectively, wherein the additional amino acid replacement is located at an amino acid position that confers less than 40% hyaluronidase activity when the amino acid position that confers less than 40% hyaluronidase activity is replaced alone in a polypeptide consisting of amino acids 38-468 of SEQ ID NO: 6 and the amino acid replacement.
Regarding instant claim 61, claim 66 of the reference application recites the polypeptide of claim 57, wherein the additional amino acid replacement is not at amino acid position 38, 40, 43, 44, 46, 47, 49, 50, 55, 57, 58, 59, 61, 62, 63, 70, 71, 72, 74, 76, 77, 78, 80, 81, 82, 83, 84, 85, 86, 87, 89, 93, 95, 96, 98, 102, 104, 105, 106, 107, 108, 109, 110, 112, 114, 115, 116, 117, 118, 119, 120, 121, 126,128, 129, 131, 132, 133, 134, 137, 140, 141, 173, 176, 177, 178, 180, 181, 182, 184, 185, 187, 188, 189, 191, 192, 193, 194, 195, 196, 197, 199, 200, 201, 202, 204, 241, 243, 244, 250, 251, 252, 254, 255, 256, 257, 259, 265, 266, 267, 269, 270, 272, 273, 274, 275, 298, 300, 301, 302, 304, 305, 306, 307, 308, 309, 311, 313, 315, 322, 323, 325, 326, 329, 332, 333, 335, 336, 337, 338, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 352, 353, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, or 366.
Regarding instant claims 63-65, claims 59-61 of the reference application recite the polypeptide of claim 58, wherein the polypeptide consists of 5, 10, or 15 amino acid replacements, respectively.
Therefore, the claims of this application are unpatentable over the claims of the reference application. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Co-Pending Application No. 19/550,132
Claims 32-36, 45, 48, 50, 54-58, 60, 61, and 63-65 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 12, 15, 18, 20, 23, 24-26, 28, and 32-36 of co-pending application no. 19/550,132 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other for reasons that follow.
Regarding instant claims 55-58 and 60, claim 1 of the reference application recites a polypeptide comprising amino acids 3-433 of SEQ ID NO: 35,
wherein the polypeptide does not comprise amino acids 1-37 of SEQ ID NO: 6,
wherein the polypeptide does not comprise amino acids 469-509 of SEQ ID NO: 6, and
wherein the polypeptide comprises at least one amino acid replacement located at amino acid position
3, 5, 8, 9, 11, 12, 14, 15, 16, 17, 18, 19, 20, 22, 23, 24, 26, 27, 28, 35, 36, 37, 39, 41, 42, 43, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 58, 60, 61, 62, 63, 64, 67, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 81, 82, 83, 84, 85, 86, 91, 93, 94, 96, 97, 98, 99, 100, 102, 105, 106, 138, 141, 142, 143, 145, 146, 147, 149, 150, 152, 153, 154, 156, 157, 158, 159, 160, 161, 162, 164, 165, 166, 167, 169, 201, 206, 208, 209, 210, 215, 216, 217, 219, 220, 221, 222, 223, 224, 225, 227, 228, 229, 230, 231, 232, 234, 235, 237, 238, 239, 240, 241, 263, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 276, 278, 279, 280, 281, 287, 288, 290, 291, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 317, 318, 319, 320, 321, 323, 324, 325, 326, 327, 328, 330, 331, 332, 335, 336, 337, 338, 339, 342, 343, 344, 345, 348, 350, 351, 353, 354, 355, 356, 359, 360, 362, 363, 366, 369, 370, 372, 373, 376, 379, 381, 382, 383, 385, 387, 388, 391, 393, 394, 395, 396, 397, 398, 399, 403, 404, 405, 406, 409, 410, 412, 414, 415, 419, 420, 422, 425, 428, 430, 432, and 433, or any combination thereof, with reference to amino acids 3-433 of SEQ ID NO: 35;
claim 35 of the reference application recites the polypeptide of claim 1, wherein the polypeptide comprising the at least one amino acid replacements has a hyaluronidase activity that is at least 40% of a hyaluronidase activity with respect to a reference polypeptide consisting of SEQ ID NO: 3;
claim 28 of the reference application recites the polypeptide of claim 1, wherein the polypeptide further comprises (i) an amino acid replacement at amino acid position 69 with reference to amino acids 3-433 of SEQ ID NO: 35, (ii) an amino acid replacement at amino acid position 70 with reference to amino acids 3-433 of SEQ ID NO: 35, and (iii) an amino acid replacement at amino acid position 166 with reference to amino acids 3-433 of SEQ ID NO: 35; and
claim 26 of the reference application recites the polypeptide of claim 1, wherein the polypeptide comprises (i) an amino acid replacement located at amino acid position 309, with reference to amino acids 3-433 of SEQ ID NO: 35, (ii) an amino acid replacement located at amino acid position 313, with reference to amino acids 3-433 of SEQ ID NO: 35, and (iii) an amino acid replacement located at amino acid position 320, with reference to amino acids 3-433 of SEQ ID NO: 35.
The sequence of amino acids 3-433 of SEQ ID NO: 3 of the reference application is identical to the sequence of amino acids 38-468 of instant SEQ ID NO: 6 and amino acid positions 69, 70, 166, 309, 313, and 320 of amino acids 3-433 of SEQ ID NO: 3 of the reference application correspond to amino acid positions 104, 105, 201, 344, 348, and 355, respectively, of amino acids 38-468 of SEQ ID NO: 6.
Regarding instant claims 32 and 45, claim 15 of the reference application recites the polypeptide of claim 1, wherein an amino acid replacement with leucine or valine is located at amino acid position 9, 41, 46, 67, 70, 79, 83, 96, 169, 208, 271, 301, 303, 309, 326, 331, 353, or a combination thereof, with reference to amino acids 3-433 of SEQ ID NO: 35.
Regarding instant claims 32, 35, and 48, claim 18 of the reference application recites the polypeptide of claim 1, wherein an amino acid replacement with leucine, tyrosine, or isoleucine is located at amino acid position 35, 310, 313, 323, or a combination thereof, with reference to amino acids 3-433 of SEQ ID NO: 35.
Regarding instant claims 33 and 50, claim 20 of the reference application recites the polypeptide of claim 1, wherein an amino acid replacement with threonine is located at amino acid position 22, 36, 39, 43, 69, 84, 145, 215, 221, 235, 308, 312, 315, 342, 359, 360, 395, 404, or a combination thereof, with reference to amino acids 3-433 of SEQ ID NO: 35.
Regarding instant claim 34, claim 23 of the reference application recites the polypeptide of claim 1, wherein an amino acid replacement with tryptophan or phenylalanine is located at amino acid position 63, 99, 288, 399, 403, or a combination thereof, with reference to amino acids 3-433 of SEQ ID NO: 35.
Regarding instant claim 36, claim 12 of the reference application recites the polypeptide of claim 1, wherein an amino acid replacement with aspartic acid is located at amino acid position 23, 156, 158, 167, 220, 324, 348, 396, 410, or a combination thereof, with reference to amino acids 3-433 of SEQ ID NO: 35.
Regarding instant claims 32 and 54, claim 24 of the reference application recites the polypeptide of claim 1, wherein an amino acid replacement with isoleucine or leucine is located at amino acid position 8, 12, 58, 73, 75, 102, 142, 166, 206, 237, 265, 272, 287, 294, 302, 351, 414, 420, 422, 428, or a combination thereof, with reference to amino acids 3-433 of SEQ IDNO: 35.
Regarding instant claim 61, claims 25 and 36 of the reference application recite the polypeptide of claim 1 or 35, wherein the additional amino acid replacement is not at amino acid position 3, 5, 8, 9, 11, 12, 14, 15, 16, 17, 18, 19, 20, 22, 23, 24, 26, 27, 28, 35, 36, 37, 39, 41, 42, 43, 45, 46, 47, 48, 49, 50, 51, 52, 54, 55, 56, 58, 60, 61, 63, 67, 69, 70, 71, 72, 73, 74, 75, 77, 79, 81, 82, 83, 84, 85, 86, 91, 93, 94, 96, 97, 98, 99, 100, 102, 105, 106, 138, 141, 142, 143, 145, 146, 147, 149, 150, 152, 153, 154, 156, 157, 158, 159, 160, 161, 162, 164, 165, 166, 167, 169, 201, 206, 208, 209, 210, 215, 216, 217, 219, 220, 221, 222, 223, 224, 225, 227, 228, 229, 230, 231, 232, 234, 235, 237, 238, 239, 240, 241, 263, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 276, 278, 279, 280, 281, 287, 288, 290, 291, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 317, 318, 319, 320, 321, 323, 324, 325, 326, 327, 328, 330, 331, 332, 335, 336, 337, 338, 339, 342, 343, 344, 345, 348, 350, 351, 353, 354, 355, 356, 359, 360, 362, 363, 366, 369, 370, 372, 373, 376, 379, 381, 382, 383, 385, 387, 388, 391, 393, 394, 395, 396, 397, 398, 399, 403, 404, 405, 406, 409, 410, 412, 414, 415, 419, 420, 422, 425, 428, 430, 432, or 433, with reference to amino acids 3-433 of SEQ ID NO: 35.
Regarding instant claims 63-65, claims 32-34 of the reference application recite the polypeptide of claim 1, wherein the polypeptide consists of 5, 10, or 15 amino acid replacements, respectively.
Therefore, the claims of this application are unpatentable over the claims of the reference application. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Co-Pending Application No. 19/550,136
Claims 32-36, 45, 48, 50, 54-58, 60, 61, and 63-65 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 12, 15, 18, 20, 23, 24, 26-28, 29-31, and 34-36 of co-pending application no. 19/550,136 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other for reasons that follow.
Regarding instant claims 55-58 and 60, claim 1 of the reference application recites a polypeptide comprising amino acids 38-468 of SEQ ID NO: 6,
wherein the polypeptide does not comprise amino acids 1-37 of SEQ ID NO: 6,
wherein the polypeptide does not comprise amino acids 469-509 of SEQ ID NO: 6, and
wherein the polypeptide comprises at least one amino acid replacement located at amino acid position 38, 40, 43, 44, 46, 47, 49, 50, 55, 57, 58, 59, 61, 62, 63, 70, 71, 72, 74, 76, 77, 78, 80, 81,82,83,84,85,86,87,89,93,95,96,98, 102,104, 105, 106, 107, 108, 109, 110, 112, 114, 115, 116, 117, 118, 119, 120, 121, 126, 128, 129, 131, 132, 133, 134, 137, 140, 141, 173, 176, 177, 178, 180, 181, 182, 184, 185, 187, 188, 189, 191, 192, 193, 194, 195, 196, 197, 199, 200, 201, 202, 204, 241, 243, 244, 250, 251, 252, 254, 255, 256, 257, 259, 265, 266, 267, 269, 270, 272, 273, 274, 275, 298, 300, 301, 302, 304, 305, 306, 307, 308, 309, 311, 313, 315, 322, 323, 325, 326, 329, 332, 333, 335, 336, 337, 338, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 352, 353, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 366, 367, or any combination thereof, with reference to amino acids 38-468 of SEQ ID NO: 6;
claim 36 of the reference application recites the polypeptide of claim 1, wherein the polypeptide comprising the at least one amino acid replacements has a hyaluronidase activity that is at least 40% of a hyaluronidase activity with respect to a reference polypeptide consisting of SEQ ID NO: 3;
claim 29 of the reference application recites the polypeptide of claim 1, wherein the polypeptide comprises (i) an amino acid replacement located at amino acid position 104, with reference to amino acids 38-468 of SEQ ID NO: 6 and (ii) an amino acid replacement located at amino acid position 105, with reference to amino acids 38-468 of SEQ ID NO: 6;
claim 30 of the reference application recites the polypeptide of claim 29, wherein the polypeptide further comprises an amino acid replacement located at amino acid position 201 with reference to amino acids 38-468 of SEQ ID NO: 6;
claim 26 of the reference application recites the polypeptide of claim 1, wherein the polypeptide comprises (i) an amino acid replacement located at amino acid position 344, with reference to amino acids 38-468 of SEQ ID NO: 6 and (ii) an amino acid replacement located at amino acid position 348, with reference to amino acids 38-468 of SEQ ID NO: 6; and
claim 27 of the reference application recites the polypeptide of claim 26, wherein the polypeptide further comprises an amino acid replacement located at amino acid position 355 with reference to amino acids 38-468 of SEQ ID NO: 6.
The sequence of amino acids 38-468 of SEQ ID NO: 6 of the reference application is identical to the sequence of amino acids 38-468 of instant SEQ ID NO: 6.
Regarding instant claims 32 and 45, claim 15 of the reference application recites the polypeptide of claim 1, wherein an amino acid replacement with leucine or valine is located at amino acid position 44, 76, 81, 102, 105, 114, 118, 131, 204, 243, 306, 336, 338, 344, 361, 366, or a combination thereof, with reference to amino acids 38-468 of SEQ ID NO: 6.
Regarding instant claims 32, 35, and 48, claim 18 of the reference application recites the polypeptide of claim 1, wherein an amino acid replacement with leucine, tyrosine, or isoleucine is located at amino acid position 70, 345, 348, 358, or a combination thereof, with reference to amino acids 38-468 of SEQ ID NO: 6.
Regarding instant claims 33 and 50, claim 20 of the reference application recites the polypeptide of claim 1, wherein an amino acid replacement with threonine is located at amino acid position 57, 71, 74, 78, 104, 119, 180, 250, 256, 270, 343, 347, 350, or a combination thereof, with reference to amino acids 38-468 of SEQ ID NO: 6.
Regarding instant claim 34, claim 23 of the reference application recites the polypeptide of claim 1, wherein an amino acid replacement with tryptophan or phenylalanine is located at amino acid position 98, 134, 323, 357, or a combination thereof, with reference to amino acids 38-468 of SEQ ID NO: 6.
Regarding instant claim 36, claim 12 of the reference application recites the polypeptide of claim 1, wherein an amino acid replacement with aspartic acid is located at amino acid position 58, 191, 193, 202, 255, 359, or a combination thereof, with reference to amino acids 38-468 of SEQ ID NO: 6.
Regarding instant claims 32 and 54, claim 24 of the reference application recites the polypeptide of claim 1, wherein an amino acid replacement with isoleucine or leucine is located at amino acid position 43, 47, 93, 108, 110, 137, 177, 201, 241, 272, 300, 307, 322, 329, 337, or a combination thereof, with reference to amino acids 38-468 of SEQ ID NO: 6.
Regarding instant claim 61, claims 28 and 31 of the reference application recite the polypeptide of claim 27 or 30, wherein the additional amino acid replacement is not at amino acid position 38, 40, 43, 44, 46, 47, 49, 50, 55, 57, 58, 59, 61, 62, 63, 70, 71, 72, 74, 76, 77, 78, 80, 81, 82, 83, 84, 85, 86, 87, 89, 93, 95, 96, 98, 102, 104, 105, 106, 107, 108, 109, 110, 112, 114, 115, 116, 117, 118, 119, 120, 121, 126,128, 129, 131, 132, 133, 134, 137, 140, 141, 173, 176, 177, 178, 180, 181, 182, 184, 185, 187, 188, 189, 191, 192, 193, 194, 195, 196, 197, 199, 200, 201, 202, 204, 241, 243, 244, 250, 251, 252, 254, 255, 256, 257, 259, 265, 266, 267, 269, 270, 272, 273, 274, 275, 298, 300, 301, 302, 304, 305, 306, 307, 308, 309, 311, 313, 315, 322, 323, 325, 326, 329, 332, 333, 335, 336, 337, 338, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 352, 353, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, or 366 or any combination thereof, with reference to amino acids 38-468 of SEQ ID NO: 6.
Regarding instant claim 63, the use of "consists" in the phrase “consists of…amino acid replacements” in claim 63 does not limit the open-ended "comprising" language in the phrase “the polypeptide comprises an amino acid replacement” in claim 55 and the phrase “polypeptide further comprises an additional amino acid replacement” in claim 60 (see MPEP 2111.03.II). As such, other than the replacement amino acids at positions 104, 105, 201, 344, 348, and 355 corresponding to amino acids 38-468 of SEQ ID NO: 6, the remaining sequence of the claimed polypeptide encompasses any amino acid modifications (i.e., amino acid substitutions, deletions, insertions, and additions) relative to amino acids 38-468 of SEQ ID NO: 6.
Regarding instant claims 64 and 65, claims 34 and 35 of the reference application recite the polypeptide of claim 33, wherein the polypeptide consists of 10 or 15 amino acid replacements, respectively.
Therefore, the claims of this application are unpatentable over the claims of the reference application. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Co-Pending Application No. 19/551,420
Claims 32-36, 45, 48, 50, 54-58, 60, 61, and 63-65 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 12, 15, 18, 20, 23, 25, and 28-32 of co-pending application no. 19/551,420 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other for reasons that follow.
Regarding instant claims 55-58 and 60, claim 1 of the reference application recites a polypeptide comprising amino acids 38-468 of SEQ ID NO: 6,
wherein the polypeptide does not comprise amino acids 1-37 of SEQ ID NO: 6,
wherein the polypeptide does not comprise amino acids 469-509 of SEQ ID NO: 6, and
wherein the polypeptide comprises at least one amino acid replacement located at amino acid position 38, 40, 43, 44, 46, 47, 49, 50, 51, 52, 53, 54, 55, 57, 58, 59, 61, 62, 63, 70, 71, 72, 74, 76, 77, 78, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 93, 95, 96, 97, 98, 99, 102, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 126, 128, 129, 131, 132, 133, 134, 135, 137, 140, 141, 173, 176, 177, 178, 180, 181, 182, 184,185, 187, 188, 189, 191, 192, 193, 194, 195, 196, 197, 199, 200, 201, 202, 204, 236, 241, 243, 244, 250, 251, 252, 254, 255, 256, 257, 258, 259, 260, 262, 263, 264, 265, 266, 267, 269, 270, 272, 273, 274, 275, 276, 298, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 311, 313, 315, 316, 322, 323, 325, 326, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 370, 371, 372, 373, 374, 377, 378, 379, 380, 383, 385, 386, 388, 389, 390, 391, 394, 395, 397, 398, 401, 404, 405, 407, 408, 411, 413, 416, 417, 418, 420, 422, 423, 426, 428, 429, 430, 431, 432, 433, 434, 438, 439, 440, 441, 444, 445, 447, 449, 450, 454, 455, 457, 460, 463, 465, 467, and 468, or any combination thereof, with reference to amino acids 38-468 of SEQ ID NO: 6;
claim 31 of the reference application recites the polypeptide of claim 1, wherein the polypeptide comprising the at least one amino acid replacements has a hyaluronidase activity that is at least 40% of a hyaluronidase activity with respect to a reference polypeptide consisting of SEQ ID NO: 3; and
claim 25 of the reference application recites the polypeptide of claim 1, wherein the polypeptide comprises amino acid replacements located at amino acid positions 104, 105, 201, 344, 348, and 355 with reference to amino acids 38-468 of SEQ ID NO: 6.
The sequence of amino acids 38-468 of SEQ ID NO: 6 of the reference application is identical to the sequence of amino acids 38-468 of instant SEQ ID NO: 6.
Regarding instant claims 32 and 45, claim 15 of the reference application recites the polypeptide of claim 1, wherein an amino acid replacement with leucine or valine is located at amino acid position 44, 76, 81, 102, 105, 114, 118, 131, 204, 243, 306, 336, 338, 344, 361, 366, or a combination thereof, with reference to amino acids 38-468 of SEQ ID NO: 6.
Regarding instant claims 32, 35, and 48, claim 18 of the reference application recites the polypeptide of claim 1, wherein an amino acid replacement with leucine, tyrosine, or isoleucine is located at amino acid position 70, 345, 348, 358, or a combination thereof, with reference to amino acids 38-468 of SEQ ID NO: 6.
Regarding instant claims 33 and 50, claim 20 of the reference application recites the polypeptide of claim 1, wherein an amino acid replacement with threonine is located at amino acid position 57, 71, 74, 78, 104, 119, 180, 250, 256, 270, 343, 347, 350, or a combination thereof, with reference to amino acids 38-468 of SEQ ID NO: 6.
Regarding instant claim 34, claim 23 of the reference application recites the polypeptide of claim 1, wherein an amino acid replacement with tryptophan or phenylalanine is located at amino acid position 98, 134, 323, 357, or a combination thereof, with reference to amino acids 38-468 of SEQ ID NO: 6.
Regarding instant claim 36, claim 12 of the reference application recites the polypeptide of claim 1, wherein an amino acid replacement with aspartic acid is located at amino acid position 58, 191, 193, 202, 255, 359, or a combination thereof, with reference to amino acids 38-468 of SEQ ID NO: 6.
Regarding instant claims 32 and 54, claim 24 of the reference application recites the polypeptide of claim 1, wherein an amino acid replacement with isoleucine or leucine is located at amino acid position 43, 47, 93, 108, 110, 137, 177, 201, 241, 272, 300, 307, 322, 329, 337, or a combination thereof, with reference to amino acids 38-468 of SEQ ID NO: 6.
Regarding instant claim 61, claim 32 of the reference application recites the polypeptide of claim 31, wherein the additional amino acid replacement is not at amino acid position 38, 40, 43, 44, 46, 47, 49, 50, 55, 57, 58, 59, 61, 62, 63, 70, 71, 72, 74, 76, 77, 78, 80, 81, 82, 83, 84, 85, 86, 87, 89, 93, 95, 96, 98, 102, 104, 105, 106, 107, 108, 109, 110, 112, 114, 115, 116, 117, 118, 119, 120,121, 126, 128, 129, 131, 132, 133, 134, 137, 140, 141, 173, 176, 177, 178, 180, 181, 182, 184,185, 187, 188, 189, 191, 192, 193, 194, 195, 196, 197, 199, 200, 201, 202, 204, 241, 243, 244, 250, 251, 252, 254, 255, 256, 257, 259, 265, 266, 267, 269, 270, 272, 273, 274, 275, 298, 300, 301, 302, 304, 305, 306, 307, 308, 309, 311, 313, 315, 322, 323, 325, 326, 329, 332, 333, 335, 336, 337, 338, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 352, 353, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 366, 370, 373, 374, 377, 378, 383, 386, 388, 391, 394, 395, 404, 408, 411,413,416,418,420,422,423,426, 428, 429, 430, 431, 432, 433, 434, 438, 439, 440, 441, 444, 445, 447, 449, 450, 454, 455, 457, 460, 463, 467, 468, or any combination thereof, with reference to amino acids 38-468 of SEQ ID NO: 6.
Regarding instant claims 63-65, claims 28-30 of the reference application recite the polypeptide of claim 33, wherein the polypeptide consists of 5, 10, or 15 amino acid replacements, respectively.
Therefore, the claims of this application are unpatentable over the claims of the reference application. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Status of the claims:
Claims 32-39, 41-43, and 45-65 are pending.
Claims 37-39, 41-43, 46, 47, 49, and 51-53 are withdrawn from consideration.
Claims 32-36, 45, 48, 50, and 54-65 are rejected.
No claim is in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID J STEADMAN whose telephone number is (571)272-0942. The examiner can normally be reached Monday to Friday, 7:30 AM to 4:00 PM.
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/David Steadman/Primary Examiner, Art Unit 1656
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