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 . In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Election/Restrictions
Applicant’s election without traverse of a formulation using the protocol of claim 3 using ZP1848, where the peptide is added as a lyophilized formulation, for the formulation of claim 27, at a batch size of 10-50L in the reply filed on 2 July, 2026 is acknowledged.
The requirement is deemed proper and is therefore made FINAL.
Applicants have elected making the formulation of claim 27 with lyophilized ZP1848 using the protocol of claim 3 at a batch size of 10-50L. A search was conducted for this invention, and references rendering it obvious were found. As a result, claims 3, 5, 13, 21, 22, 26, and 27 were examined and claims 4, 6-12, 14-21, 23-25, and 28-30 have been withdrawn from consideration. Applicants have stated that they believe all the withdrawn claims read on the election of species, but these claims describe non-elected process steps or non-elected formulation details, and so are properly withdrawn.
Claims Status
Claims 3-30 are pending.
Claims 4, 6-12, 14-21, 23-25, and 28-30 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 2 July, 2026.
Specification
The disclosure is objected to because of the following informalities: sequences are listed without their SEQ ID number, note p11, 13-15, and others. The MPEP states that "37 CFR 1.821(d) requires the use of the assigned sequence identifier in all instances where the description or claims of a patent application discuss sequences regardless of whether a given sequence is also embedded in the text of the description or claims of an application” (MPEP 2422.03).
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
first rejection
Claims 21 and 22 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 21 requires reduced foaming and/or formation of residual lumps, while claim 22 requires reduced levels of covalently linked high MW species. The issue is that the formulation/method that the foaming/lumps/covalently linked species is compared to is not defined.
second rejection
Claim 21 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 21 requires that the process “secure visual control of a clear solution.” It is not clear what this means.
third rejection
Claim 26 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 26 requires that the formulation be stable at 2-8°C for at least 18 months. There are two issues with this claim. First, the temperature is a range. If a formulation is stable at 2 degrees, but not 8 degrees, it is not clear if the limitation is met. Second, applicants have not defined “stable.” It could mean that any precipitate formed will redissolve under relatively mild conditions, it could mean that the concentration of the therapeutic does not fall below some (undefined) concentration, or some other meaning.
Claim Rejections - 35 USC § 102/35 USC § 103
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 3, 21, 22, 26, and 27 are rejected under 35 U.S.C. 102((a)(1) and/or (a)(2)) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Parshad et al (WO 2020065063, cited by applicants) with evidentiary support from Giehm et al (WO 2020065064, cited by applicants).
Parshad et al discuss formulations of GLP-2 analogs (title). These formulations are considered stable, with less than 10% degradation after storage for 18 months at 2-8°C (p4, line 6-8). These formulations generally contain the polypeptide at a concentration of about 2, 5, 10, or 20 mg/mL (p11, line 27-29). The sequence ZP1848 is specifically mentioned (p14, line 28-29), and is used in the examples (table 1, p28). Histidine is a preferred buffer, with a concentration most preferably around 15 mM (p17, line 24-27). A preferred tonicity modifier is mannitol, preferably at a concentration of 230 mM (p18, line 1-6). Arginine is used to modify the pH (p17, line 11-13). pH is about 6.2 to 6.8 (p20, line 23-24). Note that this is identical to applicant’s elected formulation. Stock solutions of excipients were prepared, mixed, a stock solution of the peptide added, the volume adjusted to 90% of desired volume, the pH adjusted with acetic acid or arginine, and the volume adjusted again to the final volume (p25, line 37, continues to p26, line 5). The reference does not state if the volume of the excipients total between 70 and 90% of the final volume or not. If it does, this reference anticipates the claims. If it does not, it differs in when additional solution is added, which is an obvious variant (MPEP 2144.04(IV)(C)).
Parshad et al discusses a process where the peptide ZP1848 is formulated by mixing a histidine buffer and mannitol, adding a solution of the peptide, making up the volume to 90% of final volume, and adding arginine to adjust the pH to between 6.2 and 6.8. If the volume of the excipients is between 70-90% of the final volume, this anticipates claim 3, otherwise, it is obvious.
It is possible to conceive of formulations/methods with more extensive foaming (such as adding a surfactant and degassing by bubbling nitrogen through the formulation), so this reference either anticipates or renders obvious claim 21.
As evidenced by Giehm et al, there is an inverse relationship between peptide concentration and the formulation of covalent oligomer formulation (abstract), so a more dilute formulation would form more high molecular weight species. Thus, the reference either anticipates or renders obvious claim 22.
Parshad et al states that the formulations are stable for 18 months at 2-8°C, either anticipating or rendering obvious claim 26.
Parshad et al describes the same concentrations as examined claim 27, and a pH range that greatly overlaps with the pH range claimed. Thus, the reference either anticipates or renders obvious claim 27.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 3, 5, 13, 21, 22, 26, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Parshad et al (WO 2020065063, cited by applicants) in view of the Herceptin package label (last revised 2000).
Parshad et al discuss formulations of GLP-2 analogs (title). These formulations are considered stable, with less than 10% degradation after storage for 18 months at 2-8°C (p4, line 6-8). These formulations generally contain the polypeptide at a concentration of about 2, 5, 10, or 20 mg/mL (p11, line 27-29). The sequence ZP1848 is specifically mentioned (p14, line 28-29), and is used in the examples (table 1, p28). Histidine is a preferred buffer, with a concentration most preferably around 15 mM (p17, line 24-27). A preferred tonicity modifier is mannitol, preferably at a concentration of 230 mM (p18, line 1-6). Arginine is used to modify the pH (p17, line 11-13). pH is about 6.2 to 6.8 (p20, line 23-24). Note that this is identical to applicant’s elected formulation. Stock solutions of excipients were prepared, mixed, a stock solution of the peptide added, the volume adjusted to 90% of desired volume, the pH adjusted with acetic acid or arginine, and the volume adjusted again to the final volume (p25, line 37, continues to p26, line 5).
As noted above, this reference anticipates or renders obvious claims 3, 21, 22, 26, and 27.
The difference between this reference and the remaining claims is that the reference does not discuss adding a lyophilized peptide, and does not discuss the scale of operation.
The Herceptin package insert states that this is an antibody that binds to EGFR2 (1st page, 2nd paragraph). It is delivered as a lyophilized powder, that is reconstituted before use (1st page, 4th paragraph, continues to 2nd page, 1st paragraph). This reference mentions dissolving a lyophilized polypeptide to make a final solution for use.
Therefore, it would be obvious to dissolve a lyophilized peptide in the method of Parshad et al, instead of the peptide in solution, as a substitution of one known element (mixing a solution) for another (mixing a lyophilized powder) yielding expected results (solution of polypeptide and excipients). As the peptide has to be dissolved at some point either way, an artisan in this field would make this modification with a reasonable expectation of success.
The Herceptin product insert renders obvious adding the polypeptide as a lyophilized powder, rendering obvious claim 5.
While neither reference discusses the scale claimed by applicants, scaling up of a prior art process capable of being scaled is not sufficient to establish patentability (MPEP 2144.04(IV)(A)). Thus, the volume limitations of claim 13 are not a patentable distinction.
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.
first rejection
Claims 3, 5, 13, 21, 22, 26, and 27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, and 19 of copending Application No. 17/276,252 (US 20220265551) in view of Parshad et al (WO 2020065063, cited by applicants) and the Herceptin package label (last revised 2000).
Competing claim 1 describes a formulation of ZP1848, with a histidine buffer, mannitol, and arginine. Competing claim 5 specifies that the formulation is stable for at least 18 months stored at 2-8°C. Competing claim 19 specifies the same formulation as examined claim 27.
The difference is that the competing claims do not specify how the formulation is made.
Parshad et al discuss formulations of GLP-2 analogs (title). Stock solutions of excipients were prepared, mixed, a stock solution of the peptide added, the volume adjusted to 90% of desired volume, the pH adjusted with acetic acid or arginine, and the volume adjusted again to the final volume (p25, line 37, continues to p26, line 5).
The Herceptin package insert states that this is an antibody that binds to EGFR2 (1st page, 2nd paragraph). It is delivered as a lyophilized powder, that is reconstituted before use (1st page, 4th paragraph, continues to 2nd page, 1st paragraph). This reference mentions dissolving a lyophilized polypeptide to make a final solution for use.
Therefore, it would be obvious to use the methodology of Parshad et al to make the formulation of the competing claims, as a substitution of one known element for another. As Parshad et al discuss almost identical formulations, an artisan in this field would attempt this process with a reasonable expectation of success.
Furthermore, it would be obvious to add the polypeptide as a lyophilized powder, as a substitution of one known element (the polypeptide solution of Parshad et al) for another (the lyophilized polypeptide of the Herceptin package insert) yielding expected results (mixed formulation). As the polypeptide is dissolved from lyophilized powder either way, an artisan in this field would attempt this modification with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
second rejection
Claims 3, 5, 13, 21, 22, and 26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 17/279,691 (US 20220031810) in view of Parshad et al (WO 2020065063, cited by applicants) and the Herceptin package label (last revised 2000).
Competing claim 1 describes a formulation of ZP1848, with a histidine buffer, mannitol, and arginine.
The difference is that the competing claims do not specify how the formulation is made.
Parshad et al discuss formulations of GLP-2 analogs (title). Stock solutions of excipients were prepared, mixed, a stock solution of the peptide added, the volume adjusted to 90% of desired volume, the pH adjusted with acetic acid or arginine, and the volume adjusted again to the final volume (p25, line 37, continues to p26, line 5).
The Herceptin package insert states that this is an antibody that binds to EGFR2 (1st page, 2nd paragraph). It is delivered as a lyophilized powder, that is reconstituted before use (1st page, 4th paragraph, continues to 2nd page, 1st paragraph). This reference mentions dissolving a lyophilized polypeptide to make a final solution for use.
Therefore, it would be obvious to use the methodology of Parshad et al to make the formulation of the competing claims, as a substitution of one known element for another. As Parshad et al discuss almost identical formulations, an artisan in this field would attempt this process with a reasonable expectation of success.
Furthermore, it would be obvious to add the polypeptide as a lyophilized powder, as a substitution of one known element (the polypeptide solution of Parshad et al) for another (the lyophilized polypeptide of the Herceptin package insert) yielding expected results (mixed formulation). As the polypeptide is dissolved from lyophilized powder either way, an artisan in this field would attempt this modification with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658
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