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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 6/2/2026 has been entered.
Claim Status
Claims 1, 3, 6, 8, 15-16, 18, 22, 29 and 32-34 are pending. Claims 1, 3, 6, 8, 15-16, 18, 22, 29 and 32-34 are being examined in this application. In the response to the restriction requirement, Applicants elected Group I, SEQ ID NO: 3 and chronic hepatitis B virus infection.
Response to Amendment
The declaration under 37 CFR 1.132 filed on 6/2/2026 is insufficient to overcome the rejection of claims 1, 3, 6, 8, 15-16, 18, 22, 29 and 32-34 based upon 35 U.S.C. 103 as set forth in the last Office action.
Applicant argues that “[A]lthough tree shrews (Tupaia belangeri) is an established animal model for hepatitis B virus (HBV) infection, there are differences in the expression of the target receptor, sodium taurocholate cotransporting polypeptide (NTCP), between humans and animal subjects, e.g., tree shrews. In the phylogenetic tree, the tree shrew forms an independent branch outside the main primate lineage. The core differences in NTCP sequences between tree shrew and human are concentrated in the two key regions critical for HBV entry (residues 84-87 and 157-165), with an overall sequence similarity of 83.9%. Only human NTCP supports successful HBV infection. Wild-type NTCPs from non-human primates such as squirrel monkeys and marmosets fail to support infection, even though their NTCP sequences share higher similarity with the human counterpart”.
Applicant also argues that “[T]here is no reference standard for equivalent dose calculation based on data from tree shrew. And, importantly, saturating dose has never been determined in tree shrews. Therefore, a saturating dose for hepalatide in human being could not have been determined, let alone expected, based on study results from tree shrews”.
Applicant further argues that “[F]rom a clinical point of view, it is preferable that the target would be blocked with entry inhibitor as completely as possible. Thus, determination of the target saturation level will help to optimize clinical protocol and reach the drug potential. In fact, a saturation dose level of one drug cannot be determined by one given dose in general. The establishment of saturation dose need an appropriate clinical design, in which there should be 2-3 dosage groups lower and higher than the saturation dose, respectively. After the drug is injected to one subject, it circulates with the blood stream. Because of the specific affinity to receptors expressed in the liver, only very low level of serum drug concentration can be detected when the receptors in the liver is unsaturated. After the receptors are saturated, a gradually increasing serum drug concentration can be detected with the increasing dosage. In other words, the saturation level is determined by the change of serum level of the drug, which, however, cannot be determined by only one dosage or a simple clinical design containing several random dosages. Therefore, it is not obvious to obtain or determine a saturating dose of a given drug merely based on the results from an animal study, or to produce a saturating level of the given drug in the liver target organ with desired safety”.
Applicant’s arguments have been fully considered but are not persuasive.
First of all, the claims require that a single dosage of 6.3-10.5 mg of a polypeptide selected from SEQ ID NOs: 21-40 is administered to a subject having or suffering from hepatitis B virus-related liver diseases. The saturating level of the polypeptide is inherently reached once a single dosage of 6.3-10.5 mg of the polypeptide is administered to said subject.
As discussed in the rejection below, Liu teaches that the effective dose for an adult human of 60kg is 4.2 mg (para [0060]).
Furthermore, the MPEP 2144.05 A states that "[G]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997)".
Since Applicant has not disclosed that the specific limitations recited in the
instant claims are for any particular purpose or solve any stated problem, absent
unexpected results, it would have been obvious for one of ordinary skill to discover the
optimum workable dosage and time interval between dosages by normal optimization
procedures known in the pharmaceutical art.
Moreover, as evidenced by Healthline (downloaded from URL:<https://www.healthline.com/health/mens-health/average-weight-for-men>), the average weight of males in the United States is 188.6-208.1 lbs (see page 1), which corresponds to 85.54-94.39 kg.
Therefore, a physician treating males weighting 85.54-94.39 kg, would have administered 5.99-6.61 mg.
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
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.
This rejection has been modified.
Claims 1, 3, 6, 8, 15-16, 18, 22, 29 and 32-34 are rejected under 35 U.S.C. 103 as being unpatentable over Liu (WO 2015/000371) as evidenced by Healthline (downloaded from URL:<https://www.healthline.com/health/mens-health/average-weight-for-men>).
With respect to claims 1, 3 and 32-34, Liu teaches a drug formulation comprising SEQ
ID NO: 1 (claim 1). As evidenced by Liu (US 2017/0112898), SEQ ID NO: 1 consists of
the amino acid sequence GTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPNKDHWPEANQVG, which
corresponds to instantly claimed SEQ ID Nos: 3 and 23.
Liu further teaches that the drug formulation is for treating a HBV infectious
disease (claim 32).
Liu also teaches that the pharmacodynamical dose in an animal was determined
as 0.4mg/kg. As calculated by body surface area, the effective dose for an adult human
(60kg) is 4.2mg (para [0060]).
Liu additionally teaches administering at day 0, 1, 2, 3, 5, 7, 9, 11 and 13 after
infection (para [0059]).
Liu further teaches administering 0.08, 0.4 and 2 mg/kg (para [0059]).
Liu does not teach administering 6.3-105 mg of the polypeptide per day.
However, the MPEP 2144.05 A states that "[G]enerally, differences in
concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or
temperature is critical. "[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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)
(Claimed process which was performed at a temperature between 40°C and 80°C and
an acid concentration between 25% and 70% was held to be prima facie obvious over a
reference process which differed from the claims only in that the reference process was
performed at a temperature of 100°C and an acid concentration of 10%.); see also
Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or
artisans to improve upon what is already generally known provides the motivation to
determine where in a disclosed set of percentage ranges is the optimum combination of
percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed
elastomeric polyurethanes which fell within the broad scope of the references were held
to be unpatentable thereover because, among other reasons, there was no evidence of
the criticality of the claimed ranges of molecular weight or molar proportions.). For more
recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc.,
874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re
Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d
1465, 43 USPQ2d 1362 (Fed. Cir. 1997)".
Since Applicant has not disclosed that the specific limitations recited in the
instant claims are for any particular purpose or solve any stated problem, absent unexpected results, it would have been obvious for one of ordinary skill to discover the
optimum dosage and time of administration by normal optimization procedures known in
the pharmaceutical art.
Furthermore, as evidenced by Healthline, the average weight of males in the United States is 188.6-208.1 lbs (see page 1), which corresponds to 85.54-94.39 kg.
Therefore, since Liu teaches that the effective dose for a 60 kg adult human is 4.2mg (para [0060]), a physician treating male subjects weighting 85.54-94.39 kg, would have administered 5.99-6.61 mg, which encompasses the claimed range.
With respect to the limitation “reaching a saturation level of a polypeptide in the liver target organ”, it is noted that said limitation is inherent to the polypeptide and to the amount of said polypeptide being administered. As discussed above. The skilled artisan would have administered the same amount instantly administered, thus reaching a saturating level of a polypeptide in the liver target organ.
With respect to claims 6, 15-16 and 18, Liu teaches that the N-terminus of the
polypeptide is modified by myristic acid and the C-terminus is modified by amidation
(claim 1).
With respect to claim 8, Liu teaches that the HBV infectious disease comprises
chronic hepatitis, HBV related liver transplantation and blockage of HBV maternal neonatal transmission (claim 33).
With respect to claim 22, Liu teaches that the HBV infectious disease comprises
HBV related liver transplantation (claim 33). Thus, reading on the limitations "selecting a
patient having a hepatitis B-related disorder" and "the administration is before, during or
after transplantation".
With respect to claim 29, Liu teaches subcutaneous administration (paras [0035], [0059] and [0078]).
Furthermore, since Applicant has not disclosed that the specific limitations
recited in the instant claims are for any particular purpose or solve any stated problem,
absent unexpected results, it would have been obvious for one of ordinary skill to
discover the optimum dosage by normal optimization procedures known in the
pharmaceutical art.
Response to Arguments
Applicant's arguments filed on 6/2/2026 have been fully considered but they are not persuasive.
Applicant arguments have been addressed above under "Response to
Amendments" on pages 3-6.
For the reasons stated above, the rejection is maintained.
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.
This rejection is maintained.
Claims 1, 3, 6, 8, 15-16, 18 and 32-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10603352.
With respect to claims 1, 3 and 32-34, '352 teaches a drug formulation comprising SEQ ID NO: 1 (claim 1), which corresponds to instantly claimed SEQ ID Nos: 3 and 23.
'352 further teaches that the drug formulation is for treating a HBV infectious disease (column 2, lines 14-15; column 5, lines 48-50). Please note that it is proper to turn to and rely on the disclosure of a patent application to ascertain what constitutes an obvious modification. This position is supported by the courts. See In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970). The skilled artisan would have been motivated to use the drug formulation of '352 to treat a HBV infectious disease.
'352 also teaches that the formulations contain 0.25, 0.5, 1 .0, 2.0, 2.1, 4.0, 4.2, 5
or 8 mg of the polypeptide (claim 10), and further teaches the pharmacodynamical dose
in an animal was determined as 0.4mg/kg. As calculated by body surface area, the
effective dose for an adult human (60kg) is 4.2mg (Examples 4 and 13; column 6, lines
57-59; column 7, lines 25-27).
'352 further teaches that fifty adult tree shrews were grouped randomly into 5
groups, which included PBS control group, high dose group (hepalatide, 2mg/kg),
middle dose group (0.4mg/kg), low dose group (0.08mg/kg) and HBIG blocking group
(60IU/kg) (Example 4), and further teaches that the average weight of the patients is
60kg (Example 4).
'352 does not teach administering 6.3-105 mg of the polypeptide per day.
However, the MPEP 2144.05 A states that "[G]enerally, differences in
concentration or temperature will not support the patentability of subject matter
encompassed by the prior art unless there is evidence indicating such concentration or
temperature is critical. "[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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)
(Claimed process which was performed at a temperature between 40°C and 80°C and
an acid concentration between 25% and 70% was held to be prima facie obvious over a
reference process which differed from the claims only in that the reference process was
performed at a temperature of 100°C and an acid concentration of 10%.); see also
Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or
artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of
percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed
elastomeric polyurethanes which fell within the broad scope of the references were held
to be unpatentable thereover because, among other reasons, there was no evidence of
the criticality of the claimed ranges of molecular weight or molar proportions.). For more
recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc.,
874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re
Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d
1465, 43 USPQ2d 1362 (Fed. Cir. 1997)".
Since Applicant has not disclosed that the specific limitations recited in the
instant claims are for any particular purpose or solve any stated problem, absent
unexpected results, it would have been obvious for one of ordinary skill to discover the
optimum time of administration by normal optimization procedures known in the
pharmaceutical art.
Moreover, as evidenced by Healthline (downloaded from URL:<https://www.healthline.com/health/mens-health/average-weight-for-men>), the average weight of males in the United States is 188.6-208.1 lbs (see page 1), which corresponds to 85.54-94.39 kg.
Therefore, a physician treating males weighting 85.54-94.39 kg, would have administered 5.99-6.61 mg.
With respect to claims 6, 15-16 and 18, '352 teaches that the N-terminus of the
polypeptide is modified by myristic acid and the C-terminus is modified by amidation
(claim 1).
With respect to claim 8, '352 teaches treating HBV chronic infection (Example 4).
With respect to claim 29, ‘352 teaches subcutaneous administration (column 7, lines 31-34; column 12, lines 29-32; column 19, lines 52-55).
Response to Arguments
Applicant's arguments filed on 6/2/2026 have been fully considered but they are not persuasive.
Applicant arguments have been addressed above under "Response to
Amendments" on pages 3-6.
For the reasons stated above, the rejection is maintained.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SERGIO COFFA whose telephone number is (571)270-3022. The examiner can normally be reached M-F: 6AM-4PM.
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/SERGIO COFFA Ph.D./
Primary Examiner
Art Unit 1658
/SERGIO COFFA/Primary Examiner, Art Unit 1658
Prosecution Insights