DETAILED ACTION
This Action is in response to the communication filed on 12/16/2026.
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 .
Election/Restrictions
Applicant’s election of the indicated species in the reply filed on 12/22/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1, 2, 10-12, 15, 16, 19, 20, 23-25, 28, 29, 31, 35-37, 40, and 58 are under consideration as they read on the elected subject matter
Claim Rejections - 35 USC § 112
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.
Claims 1, 2, 10-12, 15, 16, 19, 20, 23-25, 28, 29, 31, 35-37, 40, and 58 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.
MPEP 2173.05 is related to “Specific Topics Related to Issues Under 35 U.S.C.112(b) or Pre-AIA 35 U.S.C. 112, Second Paragraph.” MPEP 2173.05(s) “Reference to Figures or Tables” states:
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted). (Emphasis added).
Here, claims 1, 24, 28 , 40 and 58 incorporate by reference to a table or figure, specifically claims 1, 28, 40 and 58 recite “Table 2”, claim 24 recites “Table 3.1 or Table 3.2”. Since incorporation by reference is a necessity doctrine, not for applicant’s convenience, the claims are indefinite per MPEP 2173.05(s). Claims 2, 10-12, 15, 16, 19, 20, 23, 25, 29, 31, and 35-37 are included in the rejection as they are dependent claims.
The amendment may be overcome by eliminating the incorporation by reference.
Claim 19 contains the trademark/trade name FibroScan®. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe transient elastography and, accordingly, the identification/description is indefinite.
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.
Claims 1, 2, 10-12, 15, 16, 19, 20, 23-25, 28, 29, 31, 35-37, 40, and 58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-39 of U.S. Patent No. 10,450,565. Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are drawn to a method comprising administering a pharmaceutical composition comprising an AAT RNAi drug substance described in Table 2 to a subject. It is noted that Table 2 describes a double stranded nucleic acid wherein the sense strand is (NAG37)s(invAb)sagcguuuaGfGfCfauguuuaacas(invAb) (SEQ ID NO:6), and the antisense strand is usGfsuUfaAfacaugCfcUfaAfaCfgCfsu (SEQ ID NO:2). The ‘565 patent claims an RNAi agent that has the duplex structure of AD048037 identified as having SEQ ID NO: 960 and SEQ ID NO: 1033 (see claim 12 of the ‘565 patent), wherein SEQ ID NO: 960 is an antisense strand with the sequence usGfsuUfaAfacaugCfcUfaAfaCfgCfsu (see claim 1 of ‘565), which is identical to instant SEQ ID NO: 2, and SEQ ID NO: 1033 is a sense strand with the sequence (NAG37)s(invAb)sagcguuuaGfGfCfauguuuaacas(invAb) (see claim 11), which is identical to instant SEQ ID NO: 6. All of the instant claims require administering the double stranded nucleic acid having SEQ ID NO: 2 and SEQ ID NO: 6. As such, the ‘565 patent claims a double stranded nucleic acid that is identical to the double stranded nucleic acid used in the instant claimed method. The ‘565 patent also includes claim 36 which is drawn to a method for the treatment of alpha-1 antitrypsin deficiency (AATD), including the treatment of a condition or disease caused by or attributable to AATD, the method comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising SEQ ID NOs: 960 and 1033 and a pharmaceutically acceptable excipient.
The Court of Appeals for the Federal Circuit in Pfizer Inc, v Teva pharmaceuticals USA Inc., 86 USPQ2d 1001, at page 1008 (March 2008) indicates that there is no patentable distinction between claims to a product and a method of using that product disclosed in the specification of the application and that the preclusion of such a double patenting rejection under 35 USC 121 does not apply where the present application is other than a divisional application of the patent application containing such patentably indistinct claims.
Since the ‘565 patent claims a double stranded nucleic acid that is identical to the double stranded nucleic acid used in the instantly claimed method, as well as a method of using the double stranded nucleic acid to treat a condition or disease caused by or attributable to AATD using the double stranded nucleic acid, and further considering that the present application is not a divisional application of the ‘565 patent, a non-statutory double patenting rejection over the claims of the ‘565 patent is appropriate in view of the Pfizer Inc, v Teva pharmaceuticals USA Inc. decision.
It is noted that the specific active method steps of the claims, such as the number of doses and the timing of the doses, as well as amount required by the instant claims, does not impart any structural limitation to the double stranded nucleic acid agent itself. Accordingly, the instant claims are drawn to method that utilize the exact same double stranded nucleic acid agent claimed in the ‘565 patent and the instant NSDP rejection is appropriate in view of the Pfizer Inc, v Teva pharmaceuticals USA Inc. decision.
Claims 1, 2, 10-12, 15, 16, 19, 20, 23-25, 28, 29, 31, 35-37, 40, and 58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-39 of U.S. Patent No. 11,884,920. Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are drawn to a method comprising administering a pharmaceutical composition comprising an AAT RNAi drug substance described in Table 2 to a subject. It is noted that Table 2 describes a double stranded nucleic acid wherein the sense strand is (NAG37)s(invAb)sagcguuuaGfGfCfauguuuaacas(invAb) (SEQ ID NO:6), and the antisense strand is usGfsuUfaAfacaugCfcUfaAfaCfgCfsu (SEQ ID NO:2). The ‘920 patent claims an RNAi agent identified as having SEQ ID NO: 960 and SEQ ID NO: 1279 (see claims 10 and 11 of the ‘920 patent), wherein SEQ ID NO: 960 is an antisense strand with the sequence usGfsuUfaAfacaugCfcUfaAfaCfgCfsu (see claim 10 of ‘920), which is identical to instant SEQ ID NO: 2, and SEQ ID NO: 1279 is a sense strand with the nucleotide sequence agcguuuaGfGfCfauguuuaaca and can have two (InvAb) residues and a GalNAc targeting group linked to the 5’-end (see claim 11), wherein the GalNAc targeting group can be (NAG37)s (claim 8), which is a nucleotide sequence identical to instant SEQ ID NO: 6. All of the instant claims require administering the double stranded nucleic acid having SEQ ID NO: 2 and SEQ ID NO: 6. As such, the ‘920 patent claims a double stranded nucleic acid that is identical to the double stranded nucleic acid used in the instant claimed method.
The Court of Appeals for the Federal Circuit in Pfizer Inc, v Teva pharmaceuticals USA Inc., 86 USPQ2d 1001, at page 1008 (March 2008) indicates that there is no patentable distinction between claims to a product and a method of using that product disclosed in the specification of the application and that the preclusion of such a double patenting rejection under 35 USC 121 does not apply where the present application is other than a divisional application of the patent application containing such patentably indistinct claims.
Since the ‘920 patent claims a double stranded nucleic acid that is the same double stranded nucleic acid used in the instant claimed methods, and further considering that the present application is not a divisional application of the ‘920 patent, a non-statutory double patenting rejection over the claims of the ‘920 patent is appropriate in view of the Pfizer Inc, v Teva pharmaceuticals USA Inc. decision.
It is noted that the specific the active method steps, such as the number of doses and the timing of the doses, as well as amount required by the instant claims, does not impart any structural limitation to the double stranded nucleic acid agent. Accordingly, the instant claims are drawn to method that utilize the exact same double stranded nucleic acid agent claimed in the ‘565 patent and the instant NSDP rejection is appropriate in view of the Pfizer Inc, v Teva pharmaceuticals USA Inc. decision.
Claims 1, 2, 10-12, 15, 16, 19, 20, 23-25, 28, 29, 31, 35-37, 40, and 58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 11,203,756. Although the claims at issue are not identical, they are not patentably distinct from each other.
Instant claim 1 is described in the rejections above. Claim 1 of the ‘756 patent is drawn to a method for reducing the protein level of AAT in a subject in need thereof comprising administering to the subject a pharmaceutically acceptable amount of a composition comprising an RNAi agent, wherein the RNAi agent comprises a sense strand and an antisense strand as indicated in the claim, and claim 10 requires that the RNAi agent has the duplex structure of AS04837 (SEQ ID NOs: 960/1033). It is noted that SEQ ID NO: 960 is usGfsuUfaAfacaugCfcUfaAfaCfgCfsu, as indicated in claim 8 and is identical to instant SEQ ID NO: 2, and SEQ ID NO: 1033 is (NAG37)s(invAb)sagcguuuaGfGfCfauguuuaacas(invAb) as defined in Table 7, which is identical to instant SEQ ID NO: 6. It is noted that claim 22 of the ‘756 patent requires that the subject has the homozygous PiZZ genotype, or heterozygous PiZ/+ genotype, and the specification indicates that individuals with the homozygous PiZZ genotype have severe deficiency of functional AAT, which leads to pulmonary disease (see column 1, lines 59-61 (1:59-61)). Therefore, the ‘756 patent claims a method of treating a subject that has a PiZZ genotype of AAT by administering a double stranded nucleic acid that is identical to the double stranded nucleic acid used in the instantly claimed method. Although the claims of the ‘756 patent do not explicitly indicate that the subject is a human, using the specification as a dictionary to define the subject recited in the broad claim, it is clear that the specification discloses that the subject can be a human (e.g., see 15:56-61). Although the claims of the ‘756 patent do not explicitly require any particular amount of double stranded nucleic acid agent is administered or the timing of the administrations, the specification provides guidance in this respect relevant to the broadly claimed method. For instance the specification indicates that the effective amount can be in the range of 0.25 to about 5 mg/kg of body weight per dose, or 0.5 to about 4 mg/kg of body weight per dose (see 109:36-41) and provides working examples where 3 mg/kg was administered to cynomolgus monkeys (see Examples 4-5) and 2 mg/kg was administered to PiZ mice (see Example 6). The specification also discloses mice were given subcutaneous injections of the agent every two weeks (q2w) for 8 weeks q2w (see 19:28-35). Based on the teachings provided in the ‘756 patent which is specific guidance for the claimed method, it would have been a matter of routine experimentation to determine the effective dosage in mg and the effective schedule for subcutaneous injection of the double stranded agent of the broadly claimed method of the ‘756 patent. It is also noted that the specification also indicates that patients with AAT deficiency (AATD) often develop liver diseases such as chronic hepatitis, cirrhosis, fibrosis (e.g., see 2:9-13); further teaches that the claimed method can be used to teach clinical presentations in a subject with AATD such as chronic hepatitis, cirrhosis, hepatocellular carcinoma, and fulminant hepatic failure (see 3:19-29); and also teaches that the therapeutic composition can comprise one or more additional therapeutic agents or treatments (see 15:47-50).
It is noted that MPEP2144.05 states:
“Generally, 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.")”
MPEP 804 II B 1 states:
The specification can be used as a dictionary to learn the meaning of a term in the patent claim. Toro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d 1065, 1067 (Fed. Cir. 1999)… Further, those portions of the specification which provide support for the patent claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the patent. In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970).
It is also noted that claims 10, 12, 15-16, 19, 35, 37, 40, 58 do not add limitations that change the structure of the double stranded agent used or the steps of the claimed method. It is also noted that dependent claims that only add limitations to the claimed method which relate to results that necessarily occur when performing the claimed method steps do not change the structure of the agents used or the steps required by the claimed method.
Claims 1, 2, 10-12, 15, 16, 19, 20, 23-25, 28, 29, 31, 35-37, 40, and 58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 66-89 of copending Application No. 18/530795 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are described above.
Claim 66 of the ‘795 application is drawn to an RNAi agent for inhibiting expression of AAT wherein the RNAi agent comprises a sense strand and an antisense strand; claims 75 limits the antisense strand to SEQ ID NO: 960 (usGfsuUfaAfacaugCfcUfaAfaCfgCfsu), which is identical to instant SEQ ID NO: 2; and claim 76 limits the sense strand to SEQ ID NO: 1279 (agcguuuaGfGfCfauguuuaaca) which can have two (InvAb) residues and a GalNAc targeting group linked to the 5’-end, wherein the GalNAc targeting group can be (NAG37)s (see claim 72), which is a nucleotide sequence identical to instant SEQ ID NO: 6.
All of the instant claims require administering the double stranded nucleic acid having SEQ ID NO: 2 and SEQ ID NO: 6. As such, the ‘795 application claims a double stranded nucleic acid that is identical to the double stranded nucleic acid used in the instant claimed method. The ‘795 application also includes claims which are drawn to a method for the treatment of alpha-1 antitrypsin deficiency (AATD), including the treatment of a condition or disease caused by or attributable to AATD, the method comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising SEQ ID NOs: 960 and 1033 and a pharmaceutically acceptable excipient (e.g., see claims 85-89).
The Court of Appeals for the Federal Circuit in Pfizer Inc, v Teva pharmaceuticals USA Inc., 86 USPQ2d 1001, at page 1008 (March 2008) indicates that there is no patentable distinction between claims to a product and a method of using that product disclosed in the specification of the application and that the preclusion of such a double patenting rejection under 35 USC 121 does not apply where the present application is other than a divisional application of the patent application containing such patentably indistinct claims.
Since the ‘795 application claims a double stranded nucleic acid that is identical to the double stranded nucleic acid used in the instantly claimed method, as well as a method of using the double stranded nucleic acid to treat a condition or disease caused by or attributable to AATD using the double stranded nucleic acid, and further considering that the present application is not a divisional application of the ‘795 application, a provisional non-statutory double patenting rejection over the claims of the ‘795 application is appropriate in view of the Pfizer Inc, v Teva pharmaceuticals USA Inc. decision.
It is noted that the specific active method steps of the claims, such as the number of doses and the timing of the doses, as well as amount required by the instant claims, does not impart any structural limitation to the double stranded nucleic acid agent itself. Accordingly, the instant claims are drawn to method that utilize the exact same double stranded nucleic acid agent claimed in the ‘795 application and the instant provisional NSDP rejection is appropriate in view of the Pfizer Inc, v Teva pharmaceuticals USA Inc. decision.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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 1, 2, 10-12, 15, 16, 19, 20, 23-25, 28, 29, 31, 35-37, 40, and 58 are rejected under 35 U.S.C. 103 as being obvious over U.S. Patent No. 10,450,565.
Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(1).
Regarding 35 U.S.C. 102(a)(2), the applied reference has a common 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. 102(a)(2) 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) if the same invention is not being claimed; 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 in the reference 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.
As indicted in the NSDP rejection above, The ‘565 patent claims an RNAi agent that has the duplex structure of AD048037 identified as having SEQ ID NO: 960 and SEQ ID NO: 1033 (see claim 12 of the ‘565 patent), wherein SEQ ID NO: 960 is an antisense strand with the sequence usGfsuUfaAfacaugCfcUfaAfaCfgCfsu (see claim 1 of ‘565), which is identical to instant SEQ ID NO: 2, and SEQ ID NO: 1033 is a sense strand with the sequence (NAG37)s(invAb)sagcguuuaGfGfCfauguuuaacas(invAb) (see claim 11), which is identical to instant SEQ ID NO: 6. All of the instant claims require administering the double stranded nucleic acid having SEQ ID NO: 2 and SEQ ID NO: 6. As such, the ‘565 patent claims a double stranded nucleic acid that is identical to the double stranded nucleic acid used in the instant claimed method. The ‘565 patent also includes claim 36 which is drawn to a method for the treatment of alpha-1 antitrypsin deficiency (AATD), including the treatment of a condition or disease caused by or attributable to AATD, the method comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising SEQ ID NOs: 960 and 1033 and a pharmaceutically acceptable excipient.
The specification indicates that the double stranded nucleic acid may be used to treat a subject that has a PiZZ genotype of AAT by administering a double stranded nucleic acid that is identical to the double stranded nucleic acid used in the instantly claimed method. The specification discloses that the subject can be a human (e.g., see 15:56-61). It is also noted that the specification also indicates that patients with AAT deficiency (AATD) often develop liver diseases such as chronic hepatitis, cirrhosis, fibrosis (e.g., see 2:9-13); further teaches that the claimed method can be used to teach clinical presentations in a subject with AATD such as chronic hepatitis, cirrhosis, hepatocellular carcinoma, and fulminant hepatic failure (see 3:19-29); and also teaches that the therapeutic composition can comprise one or more additional therapeutic agents or treatments (see 15:47-50).
Although the patent does not explicitly teach the specific amount of double stranded nucleic acid agent administered or the timing of the administrations that is required by the instant claims, the specification of the patent indicates that the effective amount can be in the range of 0.25 to about 5 mg/kg of body weight per dose, or 0.5 to about 4 mg/kg of body weight per dose (see 109:36-41) and provides working examples where 3 mg/kg was administered to cynomolgus monkeys (see Examples 4-5) and 2 mg/kg was administered to PiZ mice (see Example 6). The specification also discloses mice were given subcutaneous injections of the agent every two weeks (q2w) for 8 weeks q2w (see 19:28-35).
Based on the teachings provided in the specification of the patent, it would have been a matter of routine experimentation to determine the effective dosage in mg and the effective schedule for subcutaneous injection of the double stranded agent to arrive at the specific amounts and administrations required by the instant claims with a reasonable expectation of success.
It is noted that MPEP2144.05 states:
“Generally, 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.")”
It is also noted that claims 10, 12, 15-16, 19, 35, 37, 40, 58 do not add limitations that change the structure of the double stranded agent used or the steps of the claimed method. It is also noted that dependent claims that only add limitations to the claimed method which relate to results that necessarily occur when performing the claimed method steps do not change the structure of the agents used or the steps required by the claimed method.
Therefore, the claims are unpatentable as being obvious over the patent.
Claims 1, 2, 10-12, 15, 16, 19, 20, 23-25, 28, 29, 31, 35-37, 40, and 58 are rejected under 35 U.S.C. 103 as being obvious over U.S. Publication 2018/0195069 (the published application of U.S. Patent No. 10,450,565).
The ‘069 publication (as in the ‘565 patent) teaches an RNAi agent that has the duplex structure of AD048037 identified as having SEQ ID NO: 960 and SEQ ID NO: 1033 , wherein SEQ ID NO: 960 is an antisense strand with the sequence usGfsuUfaAfacaugCfcUfaAfaCfgCfsu (see [0091]), which is identical to instant SEQ ID NO: 2, and SEQ ID NO: 1033 is a sense strand with the sequence (NAG37)s(invAb)sagcguuuaGfGfCfauguuuaacas(invAb) (see [0099]), which is identical to instant SEQ ID NO: 6. All of the instant claims require administering the double stranded nucleic acid having SEQ ID NO: 2 and SEQ ID NO: 6. As such, the ‘069 publication teaches a double stranded nucleic acid that is identical to the double stranded nucleic acid used in the instant claimed method. The publication also teaches a method for the treatment of alpha-1 antitrypsin deficiency (AATD), including the treatment of a condition or disease caused by or attributable to AATD, the method comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising SEQ ID NOs: 960 and 1033 and a pharmaceutically acceptable excipient (see claims 34, 52-65, etc.).
The ‘069 publication indicates that the double stranded nucleic acid may be used to treat a subject that has a PiZZ genotype of AAT by administering a double stranded nucleic acid that is identical to the double stranded nucleic acid used in the instantly claimed method. The specification discloses that the subject can be a human (e.g., see [0006]). It is also noted that the specification also indicates that patients with AAT deficiency (AATD) often develop liver diseases such as chronic hepatitis, cirrhosis, fibrosis (e.g., see [0006]); further teaches that the claimed method can be used to teach clinical presentations in a subject with AATD such as chronic hepatitis, cirrhosis, hepatocellular carcinoma, and fulminant hepatic failure (see [0011]); and also teaches that the therapeutic composition can comprise one or more additional therapeutic agents or treatments (see claim 48).
Although the patent does not explicitly teach the specific amount of double stranded nucleic acid agent administered or the timing of the administrations that is required by the instant claims, the specification of the patent indicates that the effective amount can be in the range of 0.25 to about 5 mg/kg of body weight per dose, or 0.5 to about 4 mg/kg of body weight per dose (see [0304]) and provides working examples where 3 mg/kg was administered to cynomolgus monkeys (see Examples 4-5) and 2 mg/kg was administered to PiZ mice (see Example 6). The specification also discloses mice were given subcutaneous injections of the agent every two weeks (q2w) for 8 weeks q2w (see [0139], [0348]).
Based on the teachings provided in the specification of the patent, it would have been a matter of routine experimentation to determine the effective dosage in mg and the effective schedule for subcutaneous injection of the double stranded agent to arrive at the specific amounts and administrations required by the instant claims with a reasonable expectation of success.
It is noted that MPEP2144.05 states:
“Generally, 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.")”
It is also noted that claims 10, 12, 15-16, 19, 35, 37, 40, 58 do not add limitations that change the structure of the double stranded agent used or the steps of the claimed method. It is also noted that dependent claims that only add limitations to the claimed method which relate to results that necessarily occur when performing the claimed method steps do not change the structure of the agents used or the steps required by the claimed method.
Therefore, the claims are unpatentable as being obvious over the patent.
Claims 1, 2, 10-12, 15, 16, 19, 20, 23-25, 28, 29, 31, 35-37, 40, and 58 are rejected under 35 U.S.C. 103 as being obvious over U.S. Patent No. 11,884,920.
The applied reference has a common 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.
As indicted in the NSDP rejection above, the ‘920 patent claims an RNAi agent identified as having SEQ ID NO: 960 and SEQ ID NO: 1279 (see claims 10 and 11 of the ‘920 patent), wherein SEQ ID NO: 960 is an antisense strand with the sequence usGfsuUfaAfacaugCfcUfaAfaCfgCfsu, which is identical to instant SEQ ID NO: 2, and SEQ ID NO: 1279 is a sense strand with the nucleotide sequence agcguuuaGfGfCfauguuuaaca and can have two (InvAb) residues and a GalNAc targeting group linked to the 5’-end (see claim 11), wherein the GalNAc targeting group can be (NAG37)s (claim 8), which is a nucleotide sequence identical to instant SEQ ID NO: 6. All of the instant claims require administering the double stranded nucleic acid having SEQ ID NO: 2 and SEQ ID NO: 6. As such, the ‘920 patent claims a double stranded nucleic acid that is identical to the double stranded nucleic acid used in the instant claimed method. The patent also includes teaches a method for the treatment of alpha-1 antitrypsin deficiency (AATD), including the treatment of a condition or disease caused by or attributable to AATD, the method comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising SEQ ID NOs: 960 and 1033 and a pharmaceutically acceptable excipient. The specification indicates that the double stranded nucleic acid may be used to treat a subject that has a PiZZ genotype of AAT by administering a double stranded nucleic acid that is identical to the double stranded nucleic acid used in the instantly claimed method. The specification discloses that the subject can be a human (e.g., see 15:56-61). It is also noted that the specification also indicates that patients with AAT deficiency (AATD) often develop liver diseases such as chronic hepatitis, cirrhosis, fibrosis (e.g., see 2:9-13); further teaches that the claimed method can be used to teach clinical presentations in a subject with AATD such as chronic hepatitis, cirrhosis, hepatocellular carcinoma, and fulminant hepatic failure (see 3:19-29); and also teaches that the therapeutic composition can comprise one or more additional therapeutic agents or treatments (see 15:47-50).
Although the patent does not explicitly teach the specific amount of double stranded nucleic acid agent administered or the timing of the administrations that is required by the instant claims, the specification of the patent indicates that the effective amount can be in the range of 0.25 to about 5 mg/kg of body weight per dose, or 0.5 to about 4 mg/kg of body weight per dose (see 109:36-41) and provides working examples where 3 mg/kg was administered to cynomolgus monkeys (see Examples 4-5) and 2 mg/kg was administered to PiZ mice (see Example 6). The specification also discloses mice were given subcutaneous injections of the agent every two weeks (q2w) for 8 weeks q2w (see 19:28-35).
Based on the teachings provided in the specification of the patent, it would have been a matter of routine experimentation to determine the effective dosage in mg and the effective schedule for subcutaneous injection of the double stranded agent to arrive at the specific amounts and administrations required by the instant claims with a reasonable expectation of success.
It is noted that MPEP2144.05 states:
“Generally, 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.")”
It is also noted that claims 10, 12, 15-16, 19, 35, 37, 40, 58 do not add limitations that change the structure of the double stranded agent used or the steps of the claimed method. It is also noted that dependent claims that only add limitations to the claimed method which relate to results that necessarily occur when performing the claimed method steps do not change the structure of the agents used or the steps required by the claimed method.
Therefore, the claims are unpatentable as being obvious over the patent.
Claims 1, 2, 10-12, 15, 16, 19, 20, 23-25, 28, 29, 31, 35-37, 40, and 58 are rejected under 35 U.S.C. 103 as being obvious over U.S. Patent No. 11,203,756
The applied reference has a common 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.
As indicted in the NSDP rejection above, claim 1 of the ‘756 patent is drawn to a method for reducing the protein level of AAT in a subject in need thereof comprising administering to the subject a pharmaceutically acceptable amount of a composition comprising an RNAi agent, wherein the RNAi agent comprises a sense strand and an antisense strand as indicated in the claim, and claim 10 requires that the RNAi agent has the duplex structure of AS04837 (SEQ ID NOs: 960/1033). It is noted that SEQ ID NO: 960 is usGfsuUfaAfacaugCfcUfaAfaCfgCfsu, as indicated in claim 8 and is identical to instant SEQ ID NO: 2, and SEQ ID NO: 1033 is (NAG37)s(invAb)sagcguuuaGfGfCfauguuuaacas(invAb) as defined in Table 7, which is identical to instant SEQ ID NO: 6. It is noted that claim 22 of the ‘756 patent requires that the subject has the homozygous PiZZ genotype, or heterozygous PiZ/+ genotype, and the specification indicates that individuals with the homozygous PiZZ genotype have severe deficiency of functional AAT, which leads to pulmonary disease (see column 1, lines 59-61 (1:59-61)). Therefore, the ‘756 patent claims a method of treating a subject that has a PiZZ genotype of AAT by administering a double stranded nucleic acid that is identical to the double stranded nucleic acid used in the instantly claimed method. The specification teaches that the subject can be a human (e.g., see 15:56-61). Although the claims of the ‘756 patent do not explicitly require any particular amount of double stranded nucleic acid agent is administered or the timing of the administrations, the specification indicates that the effective amount can be in the range of 0.25 to about 5 mg/kg of body weight per dose, or 0.5 to about 4 mg/kg of body weight per dose (see 109:36-41) and provides working examples where 3 mg/kg was administered to cynomolgus monkeys (see Examples 4-5) and 2 mg/kg was administered to PiZ mice (see Example 6). The specification also discloses mice were given subcutaneous injections of the agent every two weeks (q2w) for 8 weeks q2w (see 19:28-35). Based on the teachings provided in the ‘756 patent, it would have been a matter of routine experimentation to determine the effective dosage in mg and the effective schedule for subcutaneous injection of the double stranded agent of the broadly claimed method of the ‘756 patent. It is also noted that the specification also indicates that patients with AAT deficiency (AATD) often develop liver diseases such as chronic hepatitis, cirrhosis, fibrosis (e.g., see 2:9-13); further teaches that the claimed method can be used to teach clinical presentations in a subject with AATD such as chronic hepatitis, cirrhosis, hepatocellular carcinoma, and fulminant hepatic failure (see 3:19-29); and also teaches that the therapeutic composition can comprise one or more additional therapeutic agents or treatments (see 15:47-50).
It is noted that MPEP2144.05 states:
“Generally, 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.")”
It is also noted that claims 10, 12, 15-16, 19, 35, 37, 40, 58 do not add limitations that change the structure of the double stranded agent used or the steps of the claimed method. It is also noted that dependent claims that only add limitations to the claimed method which relate to results that necessarily occur when performing the claimed method steps do not change the structure of the agents used or the steps required by the claimed method.
Therefore, the claims are unpatentable as being obvious over the patent.
Conclusion
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J. E. Angell
Primary Examiner
Art Unit 1637
/J. E. ANGELL/ Primary Examiner, Art Unit 1637
Prosecution Insights