DETAILED CORRESPONDENCE
Application Status
1. The present application is being examined under the pre-AIA first to invent provisions.
2. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/23/2025 has been entered.
3. Applicants’ amendment to the claims filed on 05/11/2026 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
4. Claims 44-51, 53-55, and 57-77 are pending.
Withdrawn Rejections
5. The written description rejection of claims 24 and 44-66 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph is withdrawn in favor of the new rejections set forth below.
6. The scope of enablement rejection of claims 24 and 44-66 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph is withdrawn in favor of the new rejections set forth below.
7. The rejection of claims 24 and 44-66 under 35 U.S.C. 101 for lack of utility is withdrawn.
Election/Restrictions
8. Applicant's election with traverse of the species corresponding to positions 69, 70, 166, 309, 313, and 320 in the reply filed on 05/11/2026 is acknowledged. The traversal is on the ground(s) that examination of the genus would not be unduly burdensome, as it is directed to variations within a single sequence framework. This is not found persuasive because as stated in the Restriction Requirement mailed on 03/26/2026, each species of mutations is a unique structure with unique function. The breadth of the claims encompasses modifications ranging from 1049 to 1066, and as such there is a significant search burden involved to examined the entire breadth of the claims.
The requirement is still deemed proper and is therefore made FINAL.
6. Claims 49-51, 53-55, 58-59, 61, 63-65, and 76 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 05/29/2026.
Claims 44-48, 57, 60, 62, 66-75 and 77 will be examined to the extent they read on the elected species corresponding to positions 69, 70, 166, 309, 313, and 320.
Information Disclosure Statement
7. The IDS filed on 12/23/2025 has been considered by the examiner and a copy of the Form PTO/SB/08 is attached to the office action.
Drawings
8. The Drawings filed on 02/25/2026 are acknowledged and accepted by the examiner.
Specification/Informalities
9. The specification is objected to because the sequence listing incorporation statement at p. 4, lines 29-31 of the specification filed 03/25/2025 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.
Claim Rejections - 35 USC § 112(b)
10. 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.
11. Claims 44-48, 57, 60, 62, 66-75 and 77 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 67 (claims 44-48, 57, 60, 62, 66, 68-75 and 77 dependent therefrom) recite “polypeptide comprising amino acids 3-433 of SEQ ID NO: 35” and “the polypeptide comprises an amino acid replacement…located at amino acid position…with reference to amino acids 3-433 of SEQ ID NO: 35”. It is unclear as to how the claimed polypeptide can simultaneously comprise amino acids 3-433 of SEQ ID NO: 35 and comprise an amino acid replacement of the recited position(s) of amino acids 3-433 of SEQ ID NO: 35. It is suggested that applicant clarify the meaning of the claim.
Claims 70, 75, and 77 depend from claim 67 and thus, claims 70, 75, and 77 incorporate all limitations of claim 67. Claims 70, 75, and 77 are 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 3-433 of SEQ ID NO: 35, 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 3-433 of SEQ ID NO: 35 and the amino acid replacement. It is suggested that applicant clarify the meanings of the claims.
Claim Rejections - 35 USC § 112(a)
12. 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.
A. Written Description
13. Claims 44-48, 57, 60, 62, 66-75 and 77 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.
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.
Claims 44-48, 57, 60, 62, 66-75 and 77 are drawn in relevant part to a polypeptide comprising amino acids 3-433 of SEQ ID NO: 35, wherein the polypeptide (i) does not comprise 1-37 of SEQ ID NO: 6 and amino acids 469-509 of SEQ ID NO: 6 and (ii) 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 3-433 of SEQ ID NO: 35 and wherein the amino acid replacement is located at amino acid position 69, 70, 166, 309, 313, and 320 or any combination thereof, with reference to amino acids 3-433 of SEQ ID NO: 35. In view of the recitation of “at least one amino acid replacement”, the claim is interpreted as included any number of additional mutations to the extent of ranging between 1049 and 1066 species, and as such the structure and function of the polypeptide are unlimited.
In this case, the specification discloses an actual reduction to practice of the following representative species of the genus of “polypeptides” as encompassed by the claims (i.e. a PH20 polypeptide having hyaluronidase activity with a single point mutation in positions corresponding to positions 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 of SEQ ID NO: 35). Other than the above disclosed species there is no other drawings or structural formulas of the infinite polypeptides of any function as encompassed by the claims. As stated above, the breadth of the claims include additional mutations and combinations of mutations of any structure and function in the range of 1049 and 1066 species.
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)."
More specific to the claimed invention, the reference of Zhang (J. Biol. Chem. 284:9433-9442, 2009; examiner cited) 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].
The reference of Singh et al. (Current Protein and Peptide Science, 2017; examiner cited) 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 reference of Zhang et al. (Structure, 2018; examiner cited) discloses that a mutation of a residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide [p. 1475, column 1].
In the Federal Circuit decision, Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337 (Fed. Cir. 2021), the courts found that for broad claims to a nucleic acid encoding a chimeric T cell receptor with a functional requirement to bind a target, “the written description must demonstrate that the applicant made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus”. In the instant case, the claims are drawn to polypeptide of unlimited structure and function, and the specification does not disclose sufficient structural features in the claimed polypeptide sequence associated with any activity to allow an ordinary artisan to distinguish which multiple mutated sequences will result in polypeptides of any activity. While a person skilled in the art might be able to embark on their own research program to find suitable multiply modified polypeptides, the four corners of the written description do not demonstrate possession of such. This analysis is consistent with AbbVie Deutschland GmbH v. Janssen Biotech, Inc., 759 F.3d 1285, 1300 (Fed. Cir. 2014) which required an inventor to show “that one has truly invented the genus, i.e. that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus”.
Given that the specification discloses only a relative few representative species of single amino acid mutations at each of positions 69, 70, 166, 309, 313, and 320 with reference to amino acids 3-433 of SEQ ID NO: 35, the specification fails to disclose even a single representative species of the claimed polypeptide, and there is a very high level of unpredictability in the art of amino acid modification, 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.
B. Scope of Enablement
14. Claims 44-48, 57, 60, 62, 66-75 and 77 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while enabling for a PH20 polypeptide having hyaluronidase activity with a single point mutation in positions corresponding to positions 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 of SEQ ID NO: 35, does not reasonably provide enablement for all polypeptides as 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 breadth of the claims: Claims 44-48, 57, 60, 62, and 66-77 are drawn in relevant part to a polypeptide comprising amino acids 3-433 of SEQ ID NO: 35, wherein the polypeptide (i) does not comprise 1-37 of SEQ ID NO: 6 and amino acids 469-509 of SEQ ID NO: 6 and (ii) 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 3-433 of SEQ ID NO: 35 and wherein the amino acid replacement is located at amino acid position 69, 70, 166, 309, 313, and 320 or any combination thereof, with reference to amino acids 3-433 of SEQ ID NO: 35. In view of the recitation of “at least one amino acid replacement”, the claim is interpreted as included any number of additional mutations to the extent of ranging between 1049 and 1066 species, and as such the structure and function of the polypeptide are unlimited.
The state of the prior art; The level of one of ordinary skill; and The level of predictability in the art: As noted above, the structure and function of the claimed polypeptide is unlimited.
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)."
More specific to the claimed invention, the reference of Zhang (J. Biol. Chem. 284:9433-9442, 2009; examiner cited) 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].
The reference of Singh et al. (Current Protein and Peptide Science, 2017; examiner cited) 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 reference of Zhang et al. (Structure, 2018; examiner cited) discloses that a mutation of a residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide [p. 1475, column 1].
The evidence of record demonstrates that identifying which of the 1049 and 1066 members of the polypeptides genus of any activity was not known in the art, and 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 following working examples of polypeptides of any function, i.e. a PH20 polypeptide having hyaluronidase activity with a single point mutation in positions corresponding to positions 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 of SEQ ID NO: 35. Other than these working examples, the specification fails to disclose any other working examples of polypeptides having multiple replacements of any activity as encompassed by the claims.
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.” In the instant case, the number is not thousands but at least 1049 different polypeptides, and as such, the quantity of experimentation would be many orders of magnitude more than that in Idenix.
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 all polypeptides of any activity with respect to a reference polypeptide comprising amino acids 3-433 of SEQ ID NO: 35 as broadly encompassed by the claims.
In view of the overly broad scope of the claims, the lack of guidance and working examples provided in the specification, the high level of unpredictability, and the state of 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).
C. New Matter
15. Claims 57, 60, 62, 66, 68, and 74 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 57, 60, 62, 66, 68, and 74 recite specific combinations of amino acid replacements. Applicant fails to show support for the specific combinations of amino acid replacements as recited in claims 57, 60, 62, 66, 68, and 74. While the original application discloses single amino acid variants of most of the amino acids of the sequence of amino acids and generically discloses “combinations of modifications” and “one or more amino acid replacements, there is no apparent descriptive support for the specific combinations recited in claims 57, 60, 62, 66, 68, and 74 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.
Double Patenting
16. 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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
17. Claims 44-48, 57, 60, 62, and 66-77 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7-9, 11-13, and 15-36 of U.S. Non-provisional Application No. 19/550,132. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1, 7-9, 11-13, and 15-36 of the ‘132 patent recite 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 compirse 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, 20, 22, 23, 24, 26, 27, 28, 35, 36, 37, 39, 41, 42, 43, 45, 46, 47, 48, 49, 50, 51, 52, 54, 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, 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, 206, 208, 209, 215, 216, 217, 219, 220, 221, 222, 224, 230, 231, 232, 234, 235, 237, 238, 239, 240, 263, 265, 266, 267, 269, 270, 271, 272, 273, 274, 276, 278, 279, 280, 287, 288, 290, 291, 294, 297, 298, 300, 301, 302, 303, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 317, 318, 320, 321, 323, 324, 325, 326, 327, 328, 331, 335, 338, 339, 342, 343, 348, 351, 353, 356, 359, 360, 369, 373, 376, 379, 381, 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, 432, 433, or any combination thereof, with reference to amino acids 3- 433 of SEQ ID NO: 35. The dependent claims of the ‘132 application further limit the polypeptide to one having a hyaluronidase activity that is at least 40% of a hyaluronidase activity with respect to a reference polypeptide consisting of SEQ ID NO: 3.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
18. Claims 44-48, 57, 60, 62, and 66-77 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 32-39, 41-43, and 45-66 of copending Application No. 19/071055. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 32-39, 41-43, and 45-66 of the ‘055 application are drawn to a polypeptide comprising amino acid sequence 38-468 of SEQ ID NO: 6, wherein 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 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. Amino acids 38-468 of SEQ ID NO: 6 are 100% identical to the claimed SEQ ID NO: 35 and the numbers recited in the claims that correspond to positions in SEQ ID NO: 6 are the identical positions recited in the current pending claims in relationship to SEQ ID NO: 35.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
19. Claims 44-48, 57, 60, 62, and 66-77 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 32-39, 41-43, and 45-65 of copending Application No. 19/071264. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 32-39, 41-43, and 45-65 of the ‘264 application are drawn to a polypeptide comprising amino acid sequence 38-468 of SEQ ID NO: 6, wherein 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 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. Amino acids 38-468 of SEQ ID NO: 6 are 100% identical to the claimed SEQ ID NO: 35 and the numbers recited in the claims that correspond to positions in SEQ ID NO: 6 are the identical positions recited in the current pending claims in relationship to SEQ ID NO: 35.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
20. Claims 44-48, 57, 60, 62, and 66-77 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 41-45, 47-48, 51, 54-57, 59-60, and 63-73 of copending Application No. 19/071092. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 41-45, 47-48, 51, 54-57, 59-60, and 63-73 of the ‘092 application are drawn to a polypeptide comprising amino acid sequence 38-332 of SEQ ID NO: 6, wherein 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 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 38-332 of SEQ ID NO: 6 and amino acids 375-468 of SEQ ID NO: 6, and wherein the amino acid replacement is located at amino acid position wherein the amino acid replacement is located at amino acid position 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, or any combination thereof, with reference to amino acids 38-468 of SEQ ID NO: 6. Amino acids 38-468 of SEQ ID NO: 6 are 100% identical to the claimed SEQ ID NO: 35 and the numbers recited in the claims that correspond to positions in SEQ ID NO: 6 are the identical positions recited in the current pending claims in relationship to SEQ ID NO: 35.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
21. Claims 44-48, 57, 60, 62, and 66-77 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7-9, 11-13, and 15-37 of copending Application No. 19/550136. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1, 7-9, 11-13, and 15-37 of the ‘136 application are drawn to a polypeptide comprising amino acid sequence 38-468 of SEQ ID NO: 6, wherein 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 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, 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, [[and]] 367, or any combination thereof, with reference to amino acids 38-468 of SEQ ID NO: 6. Amino acids 38-468 of SEQ ID NO: 6 are 100% identical to the claimed SEQ ID NO: 35 and the numbers recited in the claims that correspond to positions in SEQ ID NO: 6 are the identical positions recited in the current pending claims in relationship to SEQ ID NO: 35.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
22. Claims 44-48, 57, 60, 62, and 66-77 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 24-26 and 31-36 of copending Application No. 18/922889. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1, 12, 15-16, 18, 20, 25-27, and 30-36 of the ‘889 application are drawn to a pharmaceutical composition comprising an amino acid sequence wherein at least 95% of the residues of the amino acid sequence are identical to the residues in an amino acid sequence selected from the group consisting of SEQ ID NO: 3 and 32-66 when the amino acid sequence is aligned at positions corresponding to the sequence selected from the group consisting of SEQ ID NO: 3 and 32-66 to maximize identical residues and wherein terminal gaps are treated as non-identical; the amino acid sequence comprises an amino acid modification at a position corresponding to position 320 with reference to amino acid positions set forth in SEQ ID NO: 3; and the modification at position 320 is a replacement selected from the group consisting of E, G, H, I, K, M, N, R, S, W, Y, L, C, P, and V; and a therapeutically active agent; wherein (a) and (b) are formulated for administration in the same composition.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
23. Claims 44-48, 57, 60, 62, and 66-77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 12,600,959. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-15 of the ‘959 patent recite modified PH20 polypeptides that are encompassed by the pending claims.
Conclusion
24. Status of the claims:
Claims 44-51, 53-55, and 57-77 are pending.
Claims 49-51, 53-55, 58-59, 61, 63-65, and 76 stand withdrawn pursuant to 37 CFR 1.142(b).
Claims 44-48, 57, 60, 62, 66-75 and 77 are rejected.
No claims are in condition for an allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL J HOLLAND whose telephone number is (571)270-3537. The examiner can normally be reached Monday to Friday from 8AM to 5PM.
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/PAUL J HOLLAND/Primary Examiner, Art Unit 1656
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