DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s amendment filed on November 5, 2025 is acknowledged.
Claims 3, 4, 11, and 12 have been canceled.
Claims 1, 2, 5-10, and 13-18 are pending.
Claims 13-17 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on July 18, 2025.
Claims 1, 2, 5-10, and 18 are currently under consideration.
3. In view of applicant’s amendment, following rejections are set forth.
4. 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 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.
5. 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.
6. Claims 1, 2, 5-10, and 18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kim et al. (US 7,736,653, reference on IDS) for the reasons of record.
Kim teaches the use of immunoglobulin Fc as a carrier to a polypeptide drug. Specifically, Kim teaches Fc linked to a physiologically active polypeptide via a non-peptidyl linker, wherein the Fc is from IgG including IgG4, and the linker is PEG (e.g. see claims 1-13). In examples, Kim teaches that the Fc can have CH1, hinge, CH2, and CH3 (e.g. see col. 4 and 5). The non-peptidyl linker is a biocompatible polymer; most preferred linker is PEG (e.g. see lines 40-50 in col. 9). The polypeptide drug can be human growth hormone (hGH)-PEG-Fc conjugate (e.g. see Example 3 in col 14 and lines 20-25 in col. 21). In the examples, Kim discloses proteins such as IFNα linked to a 3.4 KDa PEG having aldehyde reactive group (identical to the PEG used in the instant specification in page 26) further linked to Fc from IgG1 including aglycosylated Fc (e.g. see Examples in col. 12-26). Kim et al. teach that the polypeptide-PEG was linked to the N-terminus of the Fc fragment (e.g. see lines 5-20 in col. 13). This method of conjugating the polypeptide-PEG including hGH-PEG to the human IgG Fc was used in all Examples.
Given that the Kim teaches protein conjugates having the same structure of the instantly claimed polypeptide-Fc conjugate, the prior art conjugate (e.g. hGH-PEG-IgG Fc) would inherently bind FcRn with the same ratio as recited in the instant claims (e.g. claims 1 and 2).
Kim teaches that hGH-PEG-Fc conjugate markedly increased in relative activity to greater than 28% compared to the native hGH. From these results, it is expected that human growth hormone linked to the immunoglobulin Fc fragment has a markedly increased serum half-life and a greatly improved in vivo pharmaceutical efficacy. In addition, it is believed that the increased activity of the immunoglobulin Fc protein conjugates of the present invention is due to the increased serum stability and preserved binding affinity to receptors due to the immunoglobulin Fc or due to the space formed by the non-peptide polymer. These effects are predicted to be applicable to immunoglobulin Fc protein conjugates coupled to other physiologically active proteins.
While the reference does not teach pH of 5.5 to 6.5 for obtaining polypeptide-PEG conjugating to the Fc region, the patentability of a product does not depend on its method of production. In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985) See MPEP 2113.
Applicant’s arguments have been fully considered but have not been found persuasive.
Applicant argues that Kim does not teach the newly added limitation of pH 5.5 to 6.5 for obtaining the conjugated.
This is not found persuasive for following reasons:
In contrast to applicant’s reliance upon the “obtained” at pH of 5.5 to 6.5, it is noted the patentability of the conjugate does not depend on its method of production. Given that Kim teach that the hGH-PEG is conjugated to the N-terminus of the Fc region that is not a binding region of FcRn, Kim’s teachings would meet the limitation of linking the physiologically active polypeptide via PEG to a portion excluding the FcRn binding region of the Fc.
As such, applicant’s arguments have not been found persuasive.
7. Claims 1, 2, 5-10, and 18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jung et al. (US 8,029,789, reference on IDS) for the reasons of record.
Jung et al. teach that the aglycosylated Fc fragment can be linked to therapeutic polypeptide via non-fusion method. Specifically, Jung et al. teach that human IgG1, IgG2, or IgG4 Fc region including CH1-hinge-CH2-CH3 is produced in E.coli host cell (e.g. see Examples 1-3 in col. 13-20). Jung et al. further teach that the therapeutic polypeptide is a human growth hormone (e.g. see lines 46-50 in col. 12). Jung et al. teaches human EPO conjugate produced by first preparing EPO-PEG complex; the PEG has an aldehyde reactive group at both end of PEG (e.g. see Example 6 in col. 21). Note that the PEG used by Jung et al. is a 3.4-KDa PEG (e.g. see lines 57-60 in col. 24) that appears to be identical to the PEG used in the instant specification (see disclosure in lines 17-20 in page 26 of the instant specification as filed). Jung et al. teach that the EPO-PEG-Fc conjugate has longer serum half life as compared to EPO without Fc conjugate or hyperglycosylated EPO (e.g. see lines 51-67 in col. 22). In Example 6, Jung et al. teach EPO:PEG molar ration of 1:10 or 1:20 and the reaction was performed at pH 6.
While Jung et al. does not specify that the EPO-PEG-Fc is obtained by reacting EPO-PEG with the Fc at a pH of 5.5 to 6.5, the patentability of a product does not depend on its method of production. In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985) See MPEP 2113.
Given that the Jung et al. teach protein conjugates having the same structure of the instantly claimed polypeptide-Fc conjugate, the prior art conjugate (e.g. EPO-PEG-IgG Fc) would inherently bind FcRn with the same ratio as recited in the instant claims (e.g. claims 1 and 2).
Applicant’s arguments have been fully considered but have not been found persuasive.
Applicant argues Jung does not disclose the pH of the reaction in linking EPO-PEG to Fc. Thus, applicant asserts that the rejection should be withdrawn.
This is not found persuasive for following reasons:
Contrary to applicant’s reliance upon the pH of 5.5 to 6.5 linking EPO-PEG to the Fc, it is noted the patentability of the conjugate does not depend on its method of production. Here, Jung et al. teach the EPO-PEG-Fc conjugate exhibited a longer serum half life than native EPO, indicating that the FcRn binding site was not blocked. Therefore, Jung’s teachings would meet the limitation of linking the physiologically active polypeptide via PEG to a portion excluding the FcRn binding region of the Fc without evidenced to the contrary.
8. 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 §§ 706.02(l)(1) - 706.02(l)(3) 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.
9. Claims 1, 2, 5-10, and 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of following US Patents for the reasons of record.
The instant claims are drawn to a physiologically active polypeptide-immunoglobulin Fc conjugate comprising a physiological active polypeptide linked to an IgG4 Fc fragment via PEG, wherein the conjugated is obtained by reacting the polypeptide-PEG with the Fc at pH of 5.5 to 6.5.
The claims 1-13 of US 7,736,653 (reference on IDS, claims are drawn to a pharmaceutical composition comprising an Fc fragment as a carrier covalently linked to a physiologically active polypeptide via a non-peptide linker);
The claims 1-11 of US 8,110,665 (reference on IDS, claims are drawn to a method of increasing in vivo duration of action of a drug comprising covalently linking the drug to an immunoglobulin Fc fragment through a non-peptide linker, wherein the drug is a physiologically active polypeptide);
The claims 1-17 of US 8,163,889 (reference on IDS, claims are drawn to a protein conjugate of a physiologically active polypeptide, e.g. human growth hormone, a non-peptide polymer PEG, and immunoglobulin G, e.g. IgG, and a method of making the protein conjugate);
The claims 1-21 of US 9,061,072 (claims are drawn to a liquid formulation of a long-acting human growth hormone conjugate comprising a human growth hormone, conjugated to an IgG Fc region via a polyethylene glycol and a method of producing the liquid formulation);
The claims 1-78 of US 9,731,031 (reference on IDS, claims are drawn to a conjugate comprising oxyntomodulin derivation comprising amino acid sequence of SEQ ID NO:24, an immunoglobulin Fc region and a non-peptidyl linker such as PEG, and a method of for treating disease by administering the conjugate);
The claims 1-4 of US 9,750,820 (reference on IDS, claims are drawn to an IgG Fc region as a drug carrier that covalently linked to a drug through a non-peptide linker including PEG);
The claims 1-17 of US 9,789,202 (reference on IDS, claims are drawn to a method of treating a cancer by administering a composition comprising an interferon alpha linked to immunoglobulin G constant region via PEG linker); and
The claims 1-26 of US 9,801,950 (claims are drawn to a liquid formulation of a insulinotropic peptide conjugate consisting essentially of the peptide conjugate linked to immunoglobulin Fc region via non peptidyl polymer including PEG, and a method for preparing the liquid formulation).
Applicant’s arguments have been fully considered but have not been found persuasive.
Applicant argues that the conflicting claims do not recite the pH that linking the polypeptide-PEG to the Fc. Thus, applicant asserts that the rejection should be withdrawn.
This is not found persuasive for following reasons:
Contrary to applicant’s arguments, note the patentability of a product does not depend on its method of production. In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985) See MPEP 2113.
Given that the claims in the US patents recite the same conjugates having the same structure as the conjugate recited in the instantly claims, the conjugate in the patented claims would inherently bind FcRn with the same ratio as recited in the instant claims (e.g. in instant claims 1 and 2).
Therefore, applicant’s arguments have not been found persuasive.
10. No claim is allowed.
11. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHUN DAHLE whose telephone number is (571)272-8142. The examiner can normally be reached Mon-Fri 6:30am-4:00pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CHUN W DAHLE/Primary Examiner, Art Unit 1641