DETAILED ACTION
The present application is being examined under the pre-AIA first to invent provisions.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/18/2025 has been entered.
Applicant’s amendment, filed on 12/18/2025 has been entered.
Claims 1-3, 10-11, 13, 16, 19, 22-34, 37, 41, 46-49 have been canceled.
Claims 51-54 have been added.
Claims 4-9, 12, 14-15, 17-18, 20-21, 35-36, 38-40, 42-45, 50-54 are pending and currently under examination as they read on a method of lowering serum LDL cholesterol in a patient comprising administering at least one anti-PCSK9 antibody.
The previous Written Description rejection under 35 USC 112 (a) has been withdrawn in view of Applicant’s amendment, filed 12/18/2025
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claims 4-9, 12, 14-15, 17-18, 20-21, 35-36, 38-40, 42-45, 50-54 are rejected under pre-AIA 35 U.S.C. 103(a) as being obvious over Jackson et al. (US 2009/0142352 A1, cited on IDS).
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 (see paragraph [0407]). Moreover, Jackson disclosed treating hyperlipidemia or cardiovascular disease (paragraph [0375]).
The difference between Jackson and the present claims is that Jackson did not teach recited the specific dosage range 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 PSCK9 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.
With regards to the limitation of “lowering serum LDL cholesterol level by at least 15%”, it is noted that there does not appear that the claim language or limitations result in a manipulative difference in the method steps when compared to the prior art disclosure. Given that the prior art taught the same or nearly the same method as recited in the present claims, one would lower serum LDL cholesterol level by at least about 15% when practicing the method taught by prior art.
Therefore, the invention, as a whole, was prima facie obvious to one of ordinary skill in the art, at the time the invention was made as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Applicant’s argument
Applicant argues that the present claims are non-obvious over prior art because the prior art does not teach or suggest lowering serum LDLC by “at least 15%. In response, it is noted that such arbitrary percent decrease is an art known variable and can be routinely optimized. For example, the prior art disclosed the following:
“A physician will be able to select an appropriate treatment indications and target lipid levels depending on the individual profile of a particular patient. One well-accepted standard for guiding treatment of hyperlipidemia is the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of the High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report, National Institutes of Health, NIH Publication No. 02-5215 (2002), the printed publication of which is hereby incorporated by reference in its entirety.” [0379]
The National Cholesterol Education Program sets guidelines for LDL cholesterol ranges as follow:
Less than 100 milligrams per deciliter (mg/dL): Optimal
100-129 mg/dL: Near or above optimal
130-159 mg/dL: Borderline high
160-189 mg/dL: High
190 mg/dL and above: Very high
For example, a patient with a LDL cholesterol of 160 mg/dL would have to decrease the level by at least 10% (or 20% or more) to a be considered optimal. Therefore, the recited “at least about 10%” would not be unexpected to one of ordinary skill in the art.
Furthermore, it is noted that administering PSCK9 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. For example, the prior art disclosed the following:
“In certain embodiments, the frequency of dosing will take into account the pharmacokinetic parameters of an antigen binding protein to PCSK9 and/or any additional therapeutic agents in the formulation used. In certain embodiments, a clinician will administer the composition until a dosage is reached that achieves the desired effect. In certain embodiments, the composition can therefore be administered as a single dose, or as two or more doses (which may or may not contain the same amount of the desired molecule) over time, or as a continuous infusion via an implantation device or catheter. Further refinement of the appropriate dosage is routinely made by those of ordinary skill in the art and is within the ambit of tasks routinely performed by them. In certain embodiments, appropriate dosages can be ascertained through use of appropriate dose-response data. In some embodiments, the amount and frequency of administration can take into account the desired cholesterol level (serum and/or total) to be obtained and the subject's present cholesterol level, LDL level, and/or LDLR levels, all of which can be obtained by methods that are well known to those of skill in the art.” [0406]
Therefore, it would have been obvious to one of ordinary skill in the art to choose a lower of reduction that is appropriate for the individual subject and optimize the frequency and dosages via routing optimization.
Furthermore, Applicant has not provided any evidence of criticality with regard to the particular dosage region.
Applicant’s argument has not been found convincing. Therefore, the rejection is maintained as it applies to amended 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 4-9, 12, 14-15, 17-18, 20-21, 35-36, 38-40, 42-45, 50-54 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, cited on IDS):
U.S. Patent
Claims
11,464,857
1-12
10,611,850
1-33
8,030,457
1-27
8,168,762
1-22
8,871,914
1-25
8,981,064
1-29
9,045,547
1-66
9,920,134
1-17
8,563,698
1-6
8,829,165
1-29
8,859,741
1-24
8,871,913
1-29
8,883,983
1-30
8,889,834
1-20
9,056,915
1-23
9,493,576
1-43
The above listed patent claims disclosed either the same anti-PCSK9 antibody or a method of using the antibody for lowering cholesterol. Therefore, it would have been obvious to use the antibody for lowering serum LDL-C at a dose of about 10-3000 mg in view of Jackson et al. for reasons discussed above (see 103).
Applicant’s request to hold the rejections in abeyance has been noted. The rejection is maintained.
Claim 4-9, 12, 14-15, 17-18, 20-21, 35-36, 38-40, 42-45, 50-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of copending Application No. 14/316,587; claims 39-59, 86-91,94-98, 100, 102-105, 107-118 of copending Application No. 13/469,032; 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 (US 2009/0142352 A1, cited on IDS).
The co-pending claims disclosed either the same anti-PCSK9 antibody or a method of using the antibody for lowering cholesterol. Therefore, it would have been obvious to use the antibody for lowering serum LDL-C at a dose of about 10-3000 mg in view of Jackson et al. for reasons discussed above (see 103).
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 (see 103). In addition, Applicant’s request to hold the rejections in abeyance has been noted. 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.
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/SHARON X WEN/ Primary Examiner, Art Unit 1641