DETAILED ACTION
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 .
The Examiner and Art Unit in charge of this application has changed. Please address future correspondence to Examiner Patricia Duffy, Art Unit 1645.
Status of Claims
Claims 1-21 are pending.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in EPO on 10/13/2022. It is noted, however, that applicant has not filed a certified copy of the EP22315238.0 application as required by 37 CFR 1.55.
Election/Restrictions
Applicant’s election of Group I (claims 1-20) in the reply filed on 12-11-2525 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)). Claim 21 is withdrawn as drawn to a non-elected invention.
Information Disclosure Statement
The information disclosure statements have been considered. Initialed copies are enclosed.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
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.
Claims 5-8 are rejected under 35 U.S.C. 112(a), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
Claim 5 and dependent claims are drawn to an antibody with a “bone targeting moiety”. The limitations of claim 6-8 are optional and as such do not limit the scope of the claims. The “bone targeting moiety” a functional characteristic of any molecule. The specification as filed provides for a single molecule the meets the claimed function, the polyarginine peptide D10 as set forth by SEQ ID NO:14. A single described moiety polyarginine peptide, D10, does not provide written description for the claimed genus of all functional equivalents unrelated by structure. The genus of moieties is vast; there is no description of any core structure that meets the functional limitation. Mere function does not describe a structure, because the specification does not provide relevant identifying characteristics, including functional characteristics when coupled with known or disclosed correlation between function and structure. The courts have held that in these instances, the specification lacks written description see Enzo Biochem Inc. v. Gen-Probe Inc. 63 USPQ2D 1609 (CAFC 2002) and University of Rochester v. G.D. Searle & Co. 69 USPQ2D 1886 (CAFC 2004). When the genus is vast and compounds are claimed by function alone and the specification lacks a known or disclosed correlation between structure and function, the written description of the specification does not convey possession of the claimed genus.
Adequate written description requires more than a mere statement that it is part of the invention. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481, 1483. In Fiddes v. Baird, claims directed to mammalian FGF’s were found unpatentable due to lack of written description for the broad class. Similarly, written description of a single polyarginine peptide sequence with bone-targeting function, fails to provide written description for the broad class. “[I]t is the specification itself that must demonstrate possession. And while the description requirement does not demand any particular form of disclosure ... or that the specification recite the claimed invention in haec verba, a description that merely renders the invention obvious does not satisfy the requirement.” Ariad Pharms., Inc. v. Eli Lilly and Co., 598 F.3d 1336, 1352 (Fed. Cir. 2010).
Claims 1-20 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
As to claim 1 and claims dependent thereon (2-20) the claims are indefinite in the reference to position 228. Positions can be calculated via a number of different methods and length of the polypeptide chain. It is unclear if the method in parenthesis is limiting on the method used or if other methods may be used. As such, the position is not unambiguously described, and the skilled artisan would not be readily apprised of the metes and bounds of the claim.
As to claim 5 and dependent claims 6-8, the term “optionally” is indefinite as it is unclear if the limitation is part of the claims. Since claim 5 does not require the presence of the poly-arginine peptide the dependent claims are not seen to properly limit the subject matter of claim 5 as the subject mater of all claims 6-8 are optional.
As to claim 8, the abbreviation “D10” is indefinite as it does not distinguish from the “D10” set forth in Qui et al US 2018/0208650. The claim is not viewed as limited to the parenthesis as it is unclear if the SEQ ID NO: is limiting or not. This issue may be resolved by amending the claims to indicated “..wherein the poly-arginine peptide is set forth in SEQ ID NO:14.”
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 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.
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.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-8 and 13-19 are rejected under 35 U.S.C. 103 as being unpatentable over Qiu et al (US 2018/0208650; of record on PTOL-1449).
Qiu et al teach methods oof treating osteogenesis imperfecta (OI) with anti-TGF-beta antibodies (paragraphs [106 and 152]) . Qiu et al teach the antibody mAb2 which comprises a hinge mutation S228P as determined by Eu numbering at specification paragraph [0175]. SEQ ID NO:2 is identical to SEQ ID NO:15.
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SEQ ID NO:3 is identical to SEQ ID NO:13.
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SEQ ID NO:3 and 13 have the S228P by EU numbering as determined by bitgene.com.
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SEQ ID NO:14, 16 and 17 comprise SEQ ID NO:3/13 and have N-terminal 10mer- of aspartic acid (Asp/D) which is a bone-targeting moiety(see specification page 1, paragraph [0008], [0083] and page 11, paragraphs [0137-0145]). Qiu et al teach that the bone targeting moiety can be attached by fusion at N- and/or C-termini of heavy and light chains of the antibody or by linkers (see paragraphs [0085], [0094-0101]. Qiu et al teach a method of treating a human patient for bone loss by administration of the anti-TGF-beta antibody to the individual ant an effective amount by reducing in TGF-beta levels or activity, a reduction in bone loss, an increase in bone density and/or an increase in bone strength (see paragraphs [0102-0103]). Qiu et al teach a method of treating osteogenesis imperfective by administering an effective amount of an anti-TGF-beta antibody of the invention alone or in combination with another therapeutic for a bone loss condition (e.g. bisphosphonates) either simultaneously or sequentially (see paragraphs [0106-0107]). The antibody can be administered by various routes including intravenous (see paragraph [0117]). Qiu et al teach that the antibody may be administered at 40, 20, or 15 mg/kg or less (such as 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 mg/kg). In some embodiments the disease may be 0.01 – 0.5 mg/kg. the dosing frequency may be for example daily, every two, three, four or five days, weekly, biweekly, triweekly, monthly, bimonthly, every three months, every six months, or every twelve months or as needed. The antibody can be administered intravenous, subcutaneous, intramuscular or any other route of administration that is appropriate for the condition and the drug formulation (see paragraph [0119]). Qiu et al differ by not teaching the dosing schedule with the amounts claimed.
However, 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 dosing and modes of administration are known to the ordinary artisan, it would have been obvious to optimize both the dosing regimens and mode of administration to meet the needs of the patient at the time the invention was made. The various dosing regimens encompassed by the instant claims were obvious at the time the invention was made, given that it was well known and practice at the time the invention was made to provide therapy based upon the condition and needs of the patient, as evidenced by the teachings of the prior art. From the teachings of the references, it was apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention as both references teach the disorders and use of the antibody. 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. "The test of obviousness is not express suggestion of the claimed invention in any or all of the references but rather what the references taken collectively would suggest to those of ordinary skill in the art presumed to be familiar with them." See In re Rosselet, 146 USPQ 183, 186 (CCPA 1965). "There is no requirement (under 35 USC 103(a)) that the prior art contain an express suggestion to combine known elements to achieve the claimed invention. Rather, the suggestion to combine may come from the prior art, as filtered through the knowledge of one skilled in the art." Motorola, Inc. v. Interdiqital Tech. Corp., 43 USPQ2d 1481, 1489 (Fed. Cir. 1997). Moreover, an obviousness determination is not the result of a rigid formula disassociated from the consideration of the facts of a case. Indeed, the common sense of those skilled in the art demonstrates why some combinations would have been obvious where others would not. See KSR Int'l Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007) ("The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results."). The administration of the antibody by the effective amount parameters necessarily provides for the therapeutic bone parameters set forth in claims 13-17 as the same antibody is administered. As to claims 5-8, it is noted that the polyarginine peptides are optional (i.e. not present) and are therefore not limiting on the claims and the poly-D (aspartate) bone-targeting moiety of the prior art reads on the claims.
Claims 9 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Qiu et al (US 2018/0208650; of record on PTOL-1449) as applied to claims 1-8 and 13-19 above and further in view of Schiavi et al (WO 2019/113123; of record on PTOL-1449).
The teachings of Qiu et al are set forth supra. Qiu et al differs by not calling out the OI type and not indicating treatment by age of the human subject.
Schiavi et al teach that TGF-beta antagonists including anti-TNF-beta antibodies can be used to treat bone disease associated with elevated TGF-beta signaling including OI wherein the OI is one of Types I-XI (see pages 167-168, claims 174-178). Schiavi et al teach that antagonists include receptor decoys and anti-TNF-beta antibodies.
It would have been prima facie obvious to one having ordinary skill in the art at the time of filing to treat any one of OI types I-XI according to the method of Qiu et al as set forth supra because Schiavi et al teach that bone disease such as OI types I-XI can be treated by TGF-beta antagonists including anti-TNF-beta antibodies and treat human adult or pediatric patients as OI was well established to be a heritable disease affecting neonates/pediatric patients and those that survive to become adults.
Claims 11 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Qiu et al (US 2018/0208650; of record on PTOL-1449) as applied to claims 1-8 and 13-19 above and further in view of Bishop et al (The Lancet, 382:1424-1432, 2013).
The teachings of Qiu et al are set forth supra. Qiu et al differs by teaching administration to pediatric patients or the specific bisphosphonate drugs, aldendronate, pamidronate, zoledronate and risedronate.
Bishop et al teach the effective treatment of oral risedronate, intravenous pamidronate in the treatment of children with osteogenesis imperfecta (see page 1424 “Interpretation”). Children were ages 4-9 and 10-15 years of age (see page 1424, column 1). Treatment provides for an increase in bone mineral density (see page 1431, column 1, first full paragraph).
It would have been prima facie obvious to one having ordinary skill in the art at the time of filing to additionally treat children of 4-15 any one of OI types according to the method of Qiu et al and combine it with the bisphosphonate drug risedronate because Qiu et al teach that the anit-TNF-beta antibody therapy can be used to treat OI and can combined with bisphosphonate drugs and Bishop et al teach oral risedronate is effective at increasing BMD and is well tolerated in children.
Claims 11, 12 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Qiu et al (US 2018/0208650; of record on PTOL-1449) as applied to claims 1-8 and 13-19 above and further in view of Chevrel et al (Journal of Bone and Mineral Research, 21(2):300-306, 2006).
The teachings of Qiu et al are set forth supra. Qiu et al differs by teaching administration to adult patients with gene mutation in COL1A1 or COL1A2 or the specific bisphosphonate drugs, aldendronate, pamidronate, zoledronate and risedronate.
Chevrel et al teach that oral alendronate in 64 adult patients 57 of whom had mutations in the genes of COL1A1 and COL1A2 (see paragraph columns 1-2 on page 301). Chevrel et al teach that oral alendronate increased BMD in the patient population having osteogenesis imperfecta (see abstract page 300). Chevrel et al teach that administration significantly decreased biochemical markers of bone turnover (see page 304, column 2, last paragraph; paragraph bridging columns 1-2 at page 305).
It would have been prima facie obvious to one having ordinary skill in the art at the time of filing to additionally treat adults having OI type 1 having mutations in the genes of COL1A1 and COL1A2 according to the method of Qiu et al and combine it with the bisphosphonate drug alendronate because Qiu et al teach that the anit-TNF-beta antibody therapy can be used to treat OI and can combined with bisphosphonate drugs and Chevrel et al teach oral alendronate is effective at increasing BMD, decreases biochemical markers of bone turnover and is well tolerated in adults.
Claims 1-9 and 11-19 are rejected under 35 U.S.C. 103 as being unpatentable over Qiu et al (US 2018/0208650; of record on PTOL-1449) as applied to claims 1-8 and 13-19 above and further in view of Lee et al (US 2024/0238415, with priority to US Provisional 63/185,967 filed May 7, 2021; of record on PTOL-1449).
The teachings of Qiu et al are set forth supra. Qiu et al differs by not teaching the poly-arginine bone-targeting peptides fused to the antibody heavy or light chain, treatment of moderate to severe OI/type IV, adult or pediatric patients and the particular bisphosphonate drugs.
Lee et al teach administration of an therapeutically effective amount of an anti-TGF-beta antibody that comprises SEQ ID NO2: and SEQ ID NO:3 having a S228P substitution by EU numbering wherein the antibody comprises a bone-targeting moiety where the bone-targeting moiety is a poly-arginine peptide is fused to the N-terminus and/or C-terminus of the heavy chain and/or at the C-terminus of the light chain and wherein the poly-arginine peptide is D10 having SEQ ID NO:14 (see page 19, claims 6-10) for the treatment of humans with osteogenesis imperfecta (OI). The antibody is identical to the antibody claimed herein. The OI is moderate-to-severe OI or type IV OI (page 19, claim 11). The patient is an adult or pediatric patient (page 19, claim 12) and the human has a mutation of the COL1A1 or COL1A2 where the mutations are glycine substitution or valine deletion (page 19, claim 13). Lee et al teach that the administration provides improvement in the bone parameters/bone turnover (see page 19, claims 14-16). Lee et al teaches further comprising a bisphosphonate wherein the bisphosphonate is alendronate, pamidronate, zoledronate and risedronate (page 19, claims 21 and 22). Lee et al teach administration of 1 mg/kg or 4 mg/kg and repeating every month, two months, three months…up to 12 months and administration by intravenous infusion (see page 19, claims 19 and 20).
It would have been prima facie obvious at the time of filing to one substitute the arginine bone targeting moiety of Lee et al for the asparagine bone targeting moiety in the method of Qiu et al because Lee et al teach poly-arginine targets bone while using the same anti-TNF-beta antibody for treatment of osteogenesis imperfecta. It is prima facie obvious to swap one bone-targeting peptide for another as they perform the identical function. Additionally, it would have been obvious to one having ordinary skill in the art at the time of filing to treat moderate-to sever-OI in a human, treat OI in an adult or pediatric patient and combine the anti-TNF-beta treatment with a bisphosphonate such as alendronate, pamidronate, zoledronate or risedronate as modified supra because Lee et al teach that the same antibody combination can be used to treat such.
Claims 1-9 and 11-19 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al (US 2024/0238415, with priority to US Provisional 63/185,967 filed May 7, 2021; of record on PTOL-1449).
Lee et al teach administration of an therapeutically effective amount of an anti-TGF-beta antibody that comprises SEQ ID NO2: and SEQ ID NO:3 having a S228P substitution by EU numbering wherein the antibody comprises a bone-targeting moiety where the bone-targeting moiety is a poly-arginine peptide is fused to the N-terminus and/or C-terminus of the heavy chain and/or at the C-terminus of the light chain and wherein the poly-arginine peptide is D10 having SEQ ID NO:14 (see page 19, claims 6-10) for the treatment of humans with osteogenesis imperfecta (OI). The antibody is identical to the antibody claimed herein. The OI is moderate-to-severe OI or type IV OI (page 19, claim 11). The patient is an adult or pediatric patient (page 19, claim 12) and the human has a mutation of the COL1A1 or COL1A2 where the mutations are glycine substitution or valine deletion (page 19, claim 13). Lee et al teach that the administration provides improvement in the bone parameters/bone turnover (see page 19, claims 14-16). Lee et al teaches further comprising a bisphosphonate wherein the bisphosphonate is alendronate, pamidronate, zoledronate and risedronate (page 19, claims 21 and 22). Lee et al teach administration of 1 mg/kg or 4 mg/kg and repeating every month, two months, three months…up to 12 months and administration by intravenous infusion (see page 19, claims 19 and 20). Lee et al differ by not teaching the dosing schedule with the amounts claimed.
However, 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 dosing and modes of administration are known to the ordinary artisan, it would have been obvious to optimize both the dosing regimens and mode of administration to meet the needs of the patient at the time the invention was made. The various dosing regimens encompassed by the instant claims were obvious at the time the invention was made, given that it was well known and practice at the time the invention was made to provide therapy based upon the condition and needs of the patient, as evidenced by the teachings of the prior art. From the teachings of the references, it was apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention as both references teach the disorders and use of the antibody. 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. "The test of obviousness is not express suggestion of the claimed invention in any or all of the references but rather what the references taken collectively would suggest to those of ordinary skill in the art presumed to be familiar with them." See In re Rosselet, 146 USPQ 183, 186 (CCPA 1965). "There is no requirement (under 35 USC 103(a)) that the prior art contain an express suggestion to combine known elements to achieve the claimed invention. Rather, the suggestion to combine may come from the prior art, as filtered through the knowledge of one skilled in the art." Motorola, Inc. v. Interdiqital Tech. Corp., 43 USPQ2d 1481, 1489 (Fed. Cir. 1997). Moreover, an obviousness determination is not the result of a rigid formula disassociated from the consideration of the facts of a case. Indeed, the common sense of those skilled in the art demonstrates why some combinations would have been obvious where others would not. See KSR Int'l Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007) ("The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results."). The administration of the antibody by the effective amount parameters necessarily provides for the therapeutic bone parameters set forth in instant claims 13-17 as the same antibody is administered.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Patricia Duffy whose telephone number is (571)272-0855. The examiner can normally be reached 8:00 am - 4 pm.
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/Patricia Duffy/Primary Examiner, Art Unit 1645