DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 1 December 2025 has been entered.
Response to Amendment
Amendments to the abstract and claims filed on 1 December 2025 are acknowledged. Claims 1, 26, and 41 are amended; claims 20, 21, 35, 36, 47, and 48 are newly canceled; and claims 53-64 are newly added. Claims 1, 2, 8-10, 14, 17, 26-28, 32, 41-44, and 53-64 are pending and are examined herein on the merits.
In response to the reply filed on 1 December 2025, the objection to the abstract is changed; objections to the claims are added; the rejections under 35 U.S.C. 112(a) are changed; rejections under 35 U.S.C. 112(b) are added; and double patenting rejections are added.
Abstract
The amendment filed 1 December 2025 is objected to under 35 U.S.C. 132(a) because it introduces new matter into the disclosure. 35 U.S.C. 132(a) states that no amendment shall introduce new matter into the disclosure of the invention. The added material which is not supported by the original disclosure is as follows:
The amendment to the abstract dated 1 December 2025 introduces new matter for the reasons set forth in the rejections under 35 U.S.C. 112(a) below, which are incorporated here by reference.
Applicant is required to cancel the new matter in the reply to this Office Action.
Claim Objections
Claims 1, 10, 26, and 46 are objected to because of the following informalities:
Regarding claims 1, 26, and 46, in the first line of the independent claims, an article ("an" or "the") must precede the first instance of "amount".
Regarding claim 10, the word "that" must be added after "is a HAase."
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1, 2, 8-10, 14, 17, 26-28, 32, 41-44, and 53-64 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.
Independent claim 1 has been amended to recite the following limitations:
contacting a sample of the xHA-L-P prodrug formulation with a hyaluronoglucosidase in a pressure cycler at a pressure of at least about 5 kilopounds per square inch (KPSI) to generate oligomeric hyaluronic acid-linker-peptide drug (oHA-L-P);
contacting the oHA-L-P with a second enzyme in a pressure cycler at a pressure of at least about 35 KPSI to generate peptide digest products of the drug;
Independent claims 26 and 41 have been amended to recite analogous limitations.
The original description supports contacting a sample of the xHA-L-P prodrug formulation with a hyaluronoglucosidase in a pressure cycler at a pressure of about 5 KPSI, about 10 KPSI or about 15 KPSI ([0022] of specification). The original description also supports cycling pressure ranging between about 5 KPSI and about 80 KPSI ("xHA and/or oHA digestion may be performed in a pressure cycler under cycling pressure ranging between about 5 KPSI and about 80 KPSI," [00107] of specification). However, the claimed pressure range of "at least 5 KPSI" has no upper limit and causes the claims to read on embodiments of greater than about 80 KPSI. Accordingly, the limitation does not meet the written description requirement.
The original description supports contacting the oHA-L-P with a second enzyme in a pressure cycler at a pressure of about 35 KPSI, about 40 KPSI or about 45 KPSI ([0023] of specification). The original description also supports cycling pressure ranging between about 5 KPSI and about 80 KPSI ("xHA and/or oHA digestion may be performed in a pressure cycler under cycling pressure ranging between about 5 KPSI and about 80 KPSI," [00107] of specification). However, the claimed pressure range of "at least 35 KPSI" has no upper limit and causes the claims to read on embodiments of greater than about 35 KPSI and greater than about 80 KPSI. Accordingly, the limitation does not meet the written description requirement.
The Courts have addressed a similar fact pattern, as described in MPEP 2163.05, III:
With respect to changing numerical range limitations, the analysis must take into account which ranges one skilled in the art would consider inherently supported by the discussion in the original disclosure. In the decision in In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976), the ranges described in the original specification included a range of "25%- 60%" and specific examples of "36%" and "50%." A corresponding new claim limitation to "at least 35%" did not meet the description requirement because the phrase "at least" had no upper limit and caused the claim to read literally on embodiments outside the "25% to 60%" range, however a limitation to "between 35% and 60%" did meet the description requirement.
Dependent claims 2, 8-10, 14, 17, 27, 28, 32, 42-44, and 53-58 are rejected for inheriting both unbounded pressure ranges of the respective independent claim.
Dependent claims 59, 61, and 63 are rejected for inheriting the unbounded range "at least about 35 KPSI" of the respective independent claim.
Dependent claims 60, 62, and 64 are rejected for inheriting the unbounded range "at least about 5 KPSI" of the respective independent claim.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 62-64 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.
Claims 62 and 64 recite the limitation "the step of contacting the oHA-L-P with a second enzyme." There is insufficient antecedent basis for this limitation in the claims.
Claim 63 recites the limitation "the step of contacting a sample of the xHA-L-P prodrug formulation with a hyaluronoglucosidase." There is insufficient antecedent basis for this limitation in the claim.
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 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.
Claims 1, 2, 8-10, 14, 17, 26-28, 32, 41-44, and 53-64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8, 14, and 20 of U.S. Patent No. US 11,796,546 (previously cited). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding instant claims 1, 26, 41, and 59-64, the patented claims recite the option that the xHA-L-P is contacted with the hyaluronoglucosidase in a pressure cycler (see patented claims 7, 13, and 19) at about 10 KPSI or about 15 KPSI (patented claims 8, 14, and 20) and the option that the oHA-L-P is contacted with the second enzyme in a pressure cycler (see patented claims 7, 13, and 19) at about 40 KPSI or about 45 KPSI (patented claims 8, 14, and 20), which anticipates the recited pressures of the instant claims.
Regarding instant claims 2 and 42, patented claims 8, 14, and 20 do not explicitly recite that the peptide digest products are between about 2 amino acids and about 100 amino acids in length. However, this is held to be either inherit or obvious over patented claim 20, which recites steps (see patented claim 15) of contacting a sample of the xHA-L-P prodrug formulation with HA lyase EC 4.2.2.1 to generate oligomeric hyaluronic acid-linker-peptide drug (oHA-L-P) and contacting the oHA-L-P with Asp-N to generate peptide digest products of the drug. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See In re Aller, 220 F.2d 454,456, 105 USPQ 233, 235 (CCPA 1955).
Regarding instant claims 8, 27, and 43, patented claims 8, 14, and 20 do not recite that the step of detecting the peptide digest products is performed by a method selected from the group consisting of one or a combination of liquid chromatography-mass spectrometry (LC-MS), liquid chromatography tandem mass spectrometry (LC-MS-MS), liquid chromatography-high resolution mass spectrometry (LC-HRMS), ultraviolet (UV) absorbance and fluorescence detection. The examiner takes official notice that at least one of the recited analytical techniques is conventional for detecting the peptide digest products. The use of a known technique to improve similar methods in the same way is likely to be obvious. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, C.). For the benefit of selecting a conventional means of detecting the peptide digest products, it would have been obvious to one of ordinary skill in the art at the time of filing to modify the patented claims such that the step of detecting the peptide digest products is performed by a method selected from the group consisting of one or a combination of liquid chromatography-mass spectrometry (LC-MS), liquid chromatography tandem mass spectrometry (LC-MS-MS), liquid chromatography-high resolution mass spectrometry (LC-HRMS), ultraviolet (UV) absorbance and fluorescence detection.
Regarding instant claims 9 and 28, patented claim 20 recites that the hyaluronoglucosidase is hyaluronate (HA) lyase EC 4.2.2.1 (see patented claim 15).
Regarding instant claim 10, patented claims 8 and 14 recite a hyaluronoglucosidase but do not recite that the hyaluronoglucosidase is a HAase [that] is selected from the group consisting of HAase 1, HAase 2, HAase 3, HAase 4, HAase 5 and HAase 6. The examiner takes official notice that at least one of HAase 1, HAase 2, HAase 3, HAase 4, HAase 5 and HAase 6 is a known example of a hyaluronoglucosidase. Choosing from a finite number of identified, predictable solutions, with a reasonable expectation for success, is likely to be obvious to a person of ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, E.).
Regarding instant claim 14, patented claim 14 recites that the oHA-L-P is contacted with an endoproteinase (see patented claim 9).
Regarding instant claims 17, 32, and 44, patented claims 8, 14, and 20 do not recite the use of an internal standard and/or wherein the amount of drug present is determined using a calibration curve. The examiner takes official notice that it is conventional, when determining the amount of an analyte, to use a calibration curve. The use of a known technique to improve similar methods in the same way is likely to be obvious. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, C.). For the benefit of selecting a conventional means of determining an amount of an analyte, it would have been obvious to one of ordinary skill in the art at the time of filing to modify the patented claims such that the amount of drug present is determined using a calibration curve. Regarding instant claims 53-58, these claims do not require that the option of the use of an internal standard recited in claims 17, 32, and 44 is mandatory. Accordingly, the difference between instant claims 53-58 and patented claims 8, 14, and 20 is obvious for at least the reason set forth regarding instant claims 17, 32, and 44.
Examiner's Comment on the Prior Art
The closest prior art of record is Baker ("Independently Tuning the Biochemical and Mechanical Properties of 3D Hyaluronan-Based Hydrogels with Oxime and Diels–Alder Chemistry to Culture Breast Cancer Spheroids," Biomacromolecules 2017; previously cited). Baker discloses quantifying peptide immobilization to crosslinked hyaluronan-based hydrogels (page 4375, right col., second para.). Hydrogels incubated overnight with peptide were washed and then subjected to hyaluronidase digestion, followed by hydrolysis of peptide using 6 N HCl at 110 °C. The resulting individual amino acids were derivatized with phenylisothiocyanate (PITC) and analyzed by UPLC (ibid.). Baker does not teach or suggest replacing the step of acid hydrolysis to individual amino acids with a step of contacting the product of hyaluronidase digestion with a second enzyme.
Response to Arguments
Applicant's arguments filed on 1 December 2025 have been considered and are not fully persuasive and/or are moot in view of the new grounds of rejection. With respect to written description support, Applicant argues the following:
Paragraph [0022] of the specification as originally filed teaches that the xHA-L-P can be contacted with the hyaluronoglucosidase in a pressure cycler, and that the pressure is the pressure cycler can be about about 5 KPSI, about 10 KPSI or about 15 KPSI. At paragraph [0023], Applicant discloses that the oHA-L-P can be contacted with a second enzyme in a pressure cycler, and that pressure in the pressure cycler can be about 35 KPSI, about 40 KPSI or about 45 KPSI.
In response, the independent claims recite pressure ranges that lack an upper limit ("at least 5 KPSI" and "at least 35 KPSI"). These unbounded ranges are not supported by the original disclosure. A similar fact pattern is discussed in MPEP 2163.05, III.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHELLE ADAMS whose telephone number is (571)270-5043. The examiner can normally be reached M, T, Th, and F, 12-4 P.M.
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/MICHELLE ADAMS/Examiner, Art Unit 1797
/JENNIFER WECKER/Primary Examiner, Art Unit 1797