The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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.
Applicant’s amendment, filed 12/23/2025, has been entered.
Claims 1-49, 52, 53 have been canceled.
Claims 70-71 have been added.
Claims 50-51, 54-71 are pending and currently under examination as they read on a method of lowering serum LDL cholesterol in a human patient diagnosed with homozygous familial hypercholesterolemia (HoFH) comprising administering at least one anti-PCSK9 antibody.
Claim Rejections - 35 USC § 103
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.
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.
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.
Claims 50-51, 54-71 are rejected under 35 U.S.C. 103 as being obvious over Jackson et al. (US 2009/0142352 A1, reference of record; cited on IDS) in view of Dias et al. (J Am Coll Cardiol 2012 60(19):1888-1898. Epub 2012 Oct 17), Clinical Trial NCT01588496 (TESLA) Version 2 date 06/22/2012 and Goldberg et al. (J Clin Lipid 2011, 5:133-140, reference of record).
The applied references have a common inventor/applicant with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Jackson et al. taught the same or nearly the same method of lowering serum cholesterol comprising administering anti-PCSK9 antibody, 21B12 (see, e.g., paragraph [0496]). It is noted that this reference is Applicant’s own work therefore, the same antibody designation would have identical sequences of the heavy and light chains and their CDRS. The prior art also taught overlapping ranges of doses as recited in the present claims (see paragraph [0405]) and various routes of administration including subcutaneous (see paragraph [0407]). Moreover, Jackson et al. taught patients with homozygous hypercholesterolemia (see paragraph [0375]) and treating those identified with family history of hypercholesterolemia with 21B12 antibody (see paragraph [0505]). With regards the limitations of “defective LDL receptor activity” and “residual LDL receptor activity of 2% to 25%”, it is noted that these are characteristics of homozygous familial hypercholesterolemia as evidenced by the instant disclosure (see specification of published application paragraph [0004]) and therefore is implicitly taught by Jackson et al. by the disclosure of homozygous hypercholesterolemia as noted above.
With regards to claim 43, it is noted that one of ordinary skill in the art would be expected to select a patient who has serum LDL-C of greater than 13 mmol/L given that the prior art taught treating familial hypercholesterolemia patients (as noted above) and that the CDC has defined FH is LDL cholesterol level over 190 mg/dL in adults (and over 160 mg/dL in children).
The difference between the present claims and Jackson is that Jackson did not teach lowering LDL-C level by at least about 20%. However, it would have been obvious to one of ordinary skill in the art to aim to lower LDL-C by at least about 20% in view of the standard guidelines for hypercholesterolemia treatment well known in the pertinent art before the effective filing date of the claimed invention. For example, Goldenberg et al. taught that for adult familial hypercholesterolemia patient, treatment should achieve a reduction of LDL-C of at least 50% (see page 136, 2.2 Treatment). Therefore, one of ordinary skill in the art would have been motivated to achieve at least 20% reduction in LDL-C with the treatment taught by Jackson et al. using PCSK9 antibody.
The difference between Jackson and the present claims is that Jackson did not teach recited dosage and frequencies of administration of the antibody. However, it would have obviously for one of ordinary skill in the art to administer the antibody at any one of the recited frequencies or dosage given the teaching by Jackson.
With regards to the limitations on administration dosage and frequency, it is noted that such manipulations routinely practiced by the ordinary artisan at the time the invention were made were known as result effective variables to increase efficacy of the treatment. It is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989) (determination of suitable dosage amounts in diuretic compositions considered a matter of routine experimentation and therefore obvious). As administering PCSK9 antibody was known and readily practiced by the ordinary artisan at the time the invention was made, it would have been obvious to optimize the frequency of administration as well as evaluating the subject for effectiveness of the treatment. Moreover, Jackson specifically taught that dosage and frequency of administration can be determined in order to achieve desired cholesterol level (see paragraphs [0405]-[0406]). Therefore, it is likely the product not of innovation but of ordinary skill and common sense.
Furthermore, one of ordinary skill in the art would have been motivated to use the PCSK9 antibody as recited in the present claims for treating HoFH and arrive at the dosage and frequency of administration as recited in view of the teachings by clinical trial TESLA and Dias et al.. In particular, TESLA (version 2 dated before the effective filing date of the present application) disclosed using the same antibody for treating patients diagnosed with HoFH (see, e.g., Official Title and Inclusion Criteria). Though TESLA did not disclose the specific dose and frequency, one of ordinary skill in the art would have been motivated to try the recited regimen in view of disclosure by Dias et al. in which another clinical trial using the same antibody for patients with heterozygous FH (HeFH) that showed at 420 mg every 4 weeks subcutaneous patients had largest decrease in LDL-C (see, e.g., Figure 3). Although Dias et al. taught treating patients with HeFH, it is not teaching away from treating HoFH because Dias did not discourage one of ordinary skill in the art to use the antibody for treating HoFH. Therefore, it would have been obvious to one of ordinary skill in the art to use the antibody for treating HoFH as taught by Jackson et al. at the dose and frequency taught by Dias in view of Dias and TESLA.
With regards to the newly added claim 70, is it noted that Jackson’s antibody is the same as what is presently claimed. Furthermore, the recited product-by-process limitation does not hold patentable weight.
With regards to the newly added claim 71, it would have been obvious to measure serum LDL-C after the administration to determine a reduction has been achieved.
Therefore, the invention, as a whole, was prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, was made as evidenced by the references, especially in the absence of evidence to the contrary.
Applicant’s arguments have been considered in full but have not been found convincing.
Applicant argues that there is no expectation of success because HoFH patients have significantly lower LDL receptor function than HeFH patients and therefore, any treatment that targets LDL receptor activity, including an anti-PCSK9 antibody, would have been expected to not work, or not work as well, in HoFH patients. In response, it is noted that although HoFH patients have lower LDL receptor function, they could still have residual LDL receptor activity up to 25% as evidenced by the instant disclosure (claim 58). The present claims do not recite any limitation on how much lower the LDL receptor function the HoFH patient must have except that they could still have up to 25% residual function. Given such, one of skill in the art would not be discourage from treating HoFH patients as there is reasonable expectation of success with these patients who could still have residual function of LDL receptor. Furthermore, given that Jackson et al. taught treating HoFH with the antibody, one of ordinary skill in the art would have been motivated to use the antibody for treatment of HoFH. Reasonable expectation of success does not require absolute certainty or predictability of success.
Therefore, the rejection is maintained as it applies to amended and newly added claims.
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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 50-51, 54-71 are rejected on the ground of nonstatutory double patenting as being unpatentable over the following in view of Jackson et al. (US 2009/0142352 A1, reference of record; cited on IDS), Dias et al. (J Am Coll Cardiol 2012 60(19):1888-1898. Epub 2012 Oct 17), Clinical Trial NCT01588496 (TESLA) Version 2 date 06/22/2012 and Goldberg et al. (J Clin Lipid 2011, 5:133-140, reference of record):
US Patent (cited in IDS)
Claims
US 11464857 B2
1-12
US 8829165 B2
1-29
US 8871913 B2
1-25
US 8883983 B2
1-30
US 8981064 B2
1-29
US 9056915 B2
1-23
US 8030457 B2
1-27
US 8563698 B2
1-6
US 8859741 B2
1-24
US 8889834 B2
1-20
US 9045547 B2
1-66
US 9493576 B2
1-43
US 10611850 B2
1-33
The patent claims listed above disclosed an anti-PCSK9 monoclonal antibody that lowers LDL cholesterol and/or method of administering the antibody to reduce LDL cholesterol. Even though the patent claims do not recite the dosage and frequency, it would have been obvious to one of ordinary skill in the art to arrive at the claimed invention in view of Jackson et al., Dias et al., TESLA, and Goldberg et al as discussed above (see 103). Therefore, the patent claims and present claims render obvious of each other.
Applicant's argument and Examiner's response are essentially same as above. Therefore, the rejection is maintained.
Claims 50-51, 54-71 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable claims 1-30 of copending Application No. 14/316,587; claims 1-21, 29-30, 33-46 of copending Application USSN 13931716; claims 2-30 of copending application USSN 17011433; claims 1-42, 44, 46-50, 52, 54-56, 60-85, 87-88, 90-91, 94-98, 100, 102-105 and 107-138 of copending application USSN 13469032; claims 118-121, 125-127, 157-164 and 170-197 of copending application USSN 13886180; claims 16-17, 20, 22-88 of copending application USSN 14562546 in view of Jackson et al. (US 2009/0142352 A1, reference of record; cited on IDS), Dias et al. (J Am Coll Cardiol 2012 60(19):1888-1898. Epub 2012 Oct 17), Clinical Trial NCT01588496 (TESLA) Version 2 date 06/22/2012 and Goldberg et al. (J Clin Lipid 2011, 5:133-140, reference of record).
The co-pending claims disclosed either the same anti-PCSK9 antibody or a method of using the antibody for lowering cholesterol. Even though the copending claims do not recite the dosage and frequency, it would have been obvious to one of ordinary skill in the art to arrive at the claimed invention in view of Jackson et al., Dias et al., TESLA, and Goldberg et al as discussed above (see 103). Therefore, the copending claims and present claims render obvious of each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant's argument and Examiner's response are essentially same as above. Therefore, the rejection is maintained.
Conclusion
No claim is allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHARON X WEN whose telephone number is (571)270-3064. The examiner can normally be reached Mon-Fri 8-5.
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/SHARON X WEN/Primary Examiner, Art Unit 1641