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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 1/27/2026 has been entered.
Claim Status
Claims 1, 7-19, 21-23, 31-34, 36-39, and 42 are pending. Claims 4-5 were canceled; claims 1 and 7 were amended; and no claims were added in the Reply filed 1/27/2026. Claims 7-19, 21-23, 31-34, and 36-39 are withdrawn. Claims 1 and 42 are presently considered.
Election/Restrictions
Applicant's election with traverse of Group I (original claims 1-11, 26,28, 29, 31, 32, and 35-37 as filed 11/09/2020) in the reply filed on 12/16/2022 was previously acknowledged. The traversal was fully considered, not found persuasive, and the requirement was made Final in the previous action for reasons of record.
The originally elected species was Example 4 (see Interview Summary attached to Action mailed 2/24/2023) as set forth at pages 59-60 of the Specification filed 11/09/2020. Example 4 was consistently understood to be a method wherein sCR1(1392)-8His and sCR1(1392)-8HisSIA were administered, individually, into mice via intravenous injection at 30 mg/kg (see, e.g., Spec. filed 11/09/2020 at Example 4 at 59-60), wherein sCR1(1392)-8His was understood to comprise instant SEQ ID NO: 3 and is SEQ ID NO: 21 (see, e.g., Spec. filed 11/09/2020 at pages 25-26, identifying the compounds utilized at Example 4).
The originally elected species elected species was previously deemed obvious in view of the prior art as applied on record (see, e.g., Action mailed 5/08/2025 at 16-27; Action mailed 10/28/2024 at 13-23; see also prior actions of record).
In the Reply filed 8/07/2025, the Applicant amended claim 1 to exclude the originally elected species of SEQ ID NO: 21 by limiting claim 1 to require administration of a sCR1 variant consisting of amino acids 42-1392 of SEQ ID NO: 1, which excludes embodiments having a HIS tag and N-terminal endogenous signal sequence as present in instant SEQ ID NO: 21, sCR1(1392)-8His, and sCR1(1392)-8HisSIA. Accordingly, the originally elected species utilizing SEQ ID NO: 21 has been excluded from the pending claim scope by Applicant amendment.
Per MPEP § 803.02(III)(A),
Should applicant, in response to a rejection of a Markush claim, overcome the rejection by amending the Markush claim to exclude the species anticipated or rendered obvious by the prior art, the amended Markush claim will be examined again. The examination will be extended to the extent necessary to determine patentability of the Markush claim. In the event prior art is found during this examination that anticipates or renders obvious the amended Markush claim, the claim will be rejected and the action can be made final…
Accordingly, examination proceeded to the claimed invention requiring the administration of a sequence “consisting of” the peptide sequence of amino acids 42-1392 of SEQ ID NO: 1, or
QCNAPEWLPFARPTNLTDEFEFPIGTYLNYECRPGYSGRPFSIICLKNSVWTGAKDRCRRKSCRNPPDPVNGMVHVIKGIQFGSQIKYSCTKGYRLIGSSSATCIISGDTVIWDNETPICDRIPCGLPPTITNGDFISTNRENFHYGSVVTYRCNPGSGGRKVFELVGEPSIYCTSNDDQVGIWSGPAPQCIIPNKCTPPNVENGILVSDNRSLFSLNEVVEFRCQPGFVMKGPRRVKCQALNKWEPELPSCSRVCQPPPDVLHAERTQRDKDNFSPGQEVFYSCEPGYDLRGAASMRCTPQGDWSPAAPTCEVKSCDDFMGQLLNGRVLFPVNLQLGAKVDFVCDEGFQLKGSSASYCVLAGMESLWNSSVPVCEQIFCPSPPVIPNGRHTGKPLEVFPFGKTVNYTCDPHPDRGTSFDLIGESTIRCTSDPQGNGVWSSPAPRCGILGHCQAPDHFLFAKLKTQTNASDFPIGTSLKYECRPEYYGRPFSITCLDNLVWSSPKDVCKRKSCKTPPDPVNGMVHVITDIQVGSRINYSCTTGHRLIGHSSAECILSGNAAHWSTKPPICQRIPCGLPPTIANGDFISTNRENFHYGSVVTYRCNPGSGGRKVFELVGEPSIYCTSNDDQVGIWSGPAPQCIIPNKCTPPNVENGILVSDNRSLFSLNEVVEFRCQPGFVMKGPRRVKCQALNKWEPELPSCSRVCQPPPDVLHAERTQRDKDNFSPGQEVFYSCEPGYDLRGAASMRCTPQGDWSPAAPTCEVKSCDDFMGQLLNGRVLFPVNLQLGAKVDFVCDEGFQLKGSSASYCVLAGMESLWNSSVPVCEQIFCPSPPVIPNGRHTGKPLEVFPFGKAVNYTCDPHPDRGTSFDLIGESTIRCTSDPQGNGVWSSPAPRCGILGHCQAPDHFLFAKLKTQTNASDFPIGTSLKYECRPEYYGRPFSITCLDNLVWSSPKDVCKRKSCKTPPDPVNGMVHVITDIQVGSRINYSCTTGHRLIGHSSAECILSGNTAHWSTKPPICQRIPCGLPPTIANGDFISTNRENFHYGSVVTYRCNLGSRGRKVFELVGEPSIYCTSNDDQVGIWSGPAPQCIIPNKCTPPNVENGILVSDNRSLFSLNEVVEFRCQPGFVMKGPRRVKCQALNKWEPELPSCSRVCQPPPEILHGEHTPSHQDNFSPGQEVFYSCEPGYDLRGAASLHCTPQGDWSPEAPRCAVKSCDDFLGQLPHGRVLFPLNLQLGAKVSFVCDEGFRLKGSSVSHCVLVGMRSLWNNSVPVCEHIFCPNPPAILNGRHTGTPSGDIPYGKEISYTCDPHPDRGMTFNLIGESTIRCTSDPHGNGVWSSPAPRCELSVR
Following extensive search and consideration, the previously claimed method utilizing a sequence “consisting of” amino acids 42-1392 of SEQ ID NO: 1, was deemed obvious (see, e.g., Action mailed 8/27/2025, passim). This non-elected species is understood to continue reading upon the amended claims filed 1/27/2026, and therefore has been examined and considered a second time, but again deemed obvious in view of the prior art as applied below.
The non-elected species is understood to read upon amended claim 1 and claim 42. However, amended claim 7 is withdrawn, as the non-elected species “consisting of” the peptide sequence of amino acids 42-1392 of SEQ ID NO: 1 is not conjugated to any identified half-life extending moiety or a further soluble complement inhibitor. Furthermore, the elected invention is understood not to read upon Group II (i.e., instant claims 12-19, 21-23, 33-34 and 38-39). Furthermore, the elected species is understood to not read upon instant claims 7-11, 31-321, and 36-372 for reasons of record.
Claims 12-19, 21-23, 33-34, and 38-39 (Group II, drawn to products) remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 12/16/2022.
Claims 7-11, 31-32, and 36-37 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 8/16/2022. The species encompassed by claims 7-11, 31-32, and 36-37 were not identified as obvious variants of the originally elected species and no evidence of record currently suggests they are obvious variants of either the originally elected species or the non-elected species presently under consideration.
Per MPEP § 803.02(III)(A), examination has not been extended to additional non-elected species at this time.
Accordingly, claims 1 and 42 are presently considered
Priority
The Foreign priority claim to AU2018901703, filed May 16, 2018, is acknowledged.
Information Disclosure Statement
The IDS filed 1/27/2026 is acknowledged and presently considered.
Claim Interpretation and Examiner Notes
For purposes of examination, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action (see, e.g., MPEP § 2111.01(IV)).
Amended claim 1 is representative of the pending claim scope and presently recites:
1. (Currently Amended) A method of inhibiting complement activity in a subject, the method comprising administering a soluble complement receptor type 1 (SCR1) variant to the subject, wherein the amino acid sequence of the sCR1 variant consists of the amino acid sequence of amino acids 42 to 1392 of SEQ ID NO: 1.
The applicable claim interpretation is discussed below. Claim interpretations set forth in the previous actions mailed 8/27/2025 and 7/31/2023 are incorporated herein, where applicable.
The preamble of claim 1, reciting “of inhibiting complement activity”, is understood to recite an intended purpose or intended use (see, e.g., MPEP § 2111.02(II)). Accordingly, any prior art embodiments or teachings disclosing the positively recited steps set forth in the body of the claim is understood to fully satisfy the preamble.
“Comprising” is an open-ended transitional term (see, e.g., MPEP § 2111.03(I)), wherein additional steps or components are not excluded. However, “‘[c]omprising’ is a term of art used in claim language which means that the named elements are essential” (see, e.g., id.; see also Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997)).
“Consisting of” excludes any elements, step, or ingredient not specified (see, e.g., MPEP § 2111.03(II)). When the phrase "consists of" appears in a clause of the body of a claim, rather than immediately following the preamble, the "consisting of" phrase limits only the element set forth in that clause; other elements are not excluded from the claim as a whole (see, e.g., MPEP § 2111.03(II)). Here, the phrase “consisting of” is understood to limit the administered sCR1 variant to the peptide “consisting of” amino acids 42-1392 of SEQ ID NO: 1, or
QCNAPEWLPFARPTNLTDEFEFPIGTYLNYECRPGYSGRPFSIICLKNSVWTGAKDRCRRKSCRNPPDPVNGMVHVIKGIQFGSQIKYSCTKGYRLIGSSSATCIISGDTVIWDNETPICDRIPCGLPPTITNGDFISTNRENFHYGSVVTYRCNPGSGGRKVFELVGEPSIYCTSNDDQVGIWSGPAPQCIIPNKCTPPNVENGILVSDNRSLFSLNEVVEFRCQPGFVMKGPRRVKCQALNKWEPELPSCSRVCQPPPDVLHAERTQRDKDNFSPGQEVFYSCEPGYDLRGAASMRCTPQGDWSPAAPTCEVKSCDDFMGQLLNGRVLFPVNLQLGAKVDFVCDEGFQLKGSSASYCVLAGMESLWNSSVPVCEQIFCPSPPVIPNGRHTGKPLEVFPFGKTVNYTCDPHPDRGTSFDLIGESTIRCTSDPQGNGVWSSPAPRCGILGHCQAPDHFLFAKLKTQTNASDFPIGTSLKYECRPEYYGRPFSITCLDNLVWSSPKDVCKRKSCKTPPDPVNGMVHVITDIQVGSRINYSCTTGHRLIGHSSAECILSGNAAHWSTKPPICQRIPCGLPPTIANGDFISTNRENFHYGSVVTYRCNPGSGGRKVFELVGEPSIYCTSNDDQVGIWSGPAPQCIIPNKCTPPNVENGILVSDNRSLFSLNEVVEFRCQPGFVMKGPRRVKCQALNKWEPELPSCSRVCQPPPDVLHAERTQRDKDNFSPGQEVFYSCEPGYDLRGAASMRCTPQGDWSPAAPTCEVKSCDDFMGQLLNGRVLFPVNLQLGAKVDFVCDEGFQLKGSSASYCVLAGMESLWNSSVPVCEQIFCPSPPVIPNGRHTGKPLEVFPFGKAVNYTCDPHPDRGTSFDLIGESTIRCTSDPQGNGVWSSPAPRCGILGHCQAPDHFLFAKLKTQTNASDFPIGTSLKYECRPEYYGRPFSITCLDNLVWSSPKDVCKRKSCKTPPDPVNGMVHVITDIQVGSRINYSCTTGHRLIGHSSAECILSGNTAHWSTKPPICQRIPCGLPPTIANGDFISTNRENFHYGSVVTYRCNLGSRGRKVFELVGEPSIYCTSNDDQVGIWSGPAPQCIIPNKCTPPNVENGILVSDNRSLFSLNEVVEFRCQPGFVMKGPRRVKCQALNKWEPELPSCSRVCQPPPEILHGEHTPSHQDNFSPGQEVFYSCEPGYDLRGAASLHCTPQGDWSPEAPRCAVKSCDDFLGQLPHGRVLFPLNLQLGAKVSFVCDEGFRLKGSSVSHCVLVGMRSLWNNSVPVCEHIFCPNPPAILNGRHTGTPSGDIPYGKEISYTCDPHPDRGMTFNLIGESTIRCTSDPHGNGVWSSPAPRCELSVR
Accordingly, “consisting of” excludes the presence of additional tags, endogenous sequences, mutations, deletions, insertions, etc. Accordingly, an sCR1 “consisting of” amino acids 42-1392 of SEQ ID NO: 1 necessarily excludes the “half-life extending moiety” or further soluble complement inhibitor as required at amended claim 7. The “consisting of” language is understood to require the exact, unmodified amino acid sequence of amino acids 42-1392 of SEQ ID NO: 1.
The term “subject” is understood to mean “any animal including humans” (see, e.g., Spec. filed 11/09/2020 at 34 at lines 4-6). The originally elected species of Example 4 utilizes mice as a subject (see, e.g., Spec. filed 11/09/2020 at 59-60 at Example 4).
The term “administering” is not explicitly defined, and is therefore reasonably understood to encompass all forms of administration, including intravenous, oral, topical, intramuscular injection, etc. The originally elected species of Example 4 utilized intravenous injection (see, e.g., Spec. filed 11/09/2020 at 59-60 at Example 4), and this exemplified form of administration is informative but not limiting.
The phrase “soluble complement receptor type 1 (SCR1) variant” was previously understood to refer to all “variants”, including (i) “truncation variants” (see, e.g., Spec. filed 11/09/2020 at 2 at lines 25-35, page 31 at lines 30-31), (ii) substitution variants (see id. at 4 at lines 25-30), (iii) deletion variants (see id. at 4 at lines 25-30, page 31 at lines 30-31), (iv) insertion variants (see id. at 4 at lines 25-30), (v) and variants including “naturally-occurring substitutions and engineered substitutions” (see id. at 4 at lines 25-30). However, the issue is moot in view of the amendments filed 8/7/2025 (and 1/27/2026) which was understood to limit the sCR1 variant to the single polypeptide “consisting of” amino acids 42 to 1392 of SEQ ID NO: 1.
The term “about” appears undefined on record, but is pertinent to the claim scope and an understanding of the specification. Examiner notes that the term “about” is understood in the biochemical arts to generally mean “within 20 percent” (see, e.g., US 2009/0028832 A13 at ¶[0111]; see also US 2009/0105341 A14 at ¶[0049]; see also US 2012/01786765 at ¶[0277]), or even more broadly “within 1 or more than 1 standard deviation” (see US 2012/0178676 A1 at ¶[0277]). Accordingly, with respect to the instant disclosure and with prior art of record, unless the term “about” is otherwise clearly defined, the term is reasonably inferred to indicate a range either “within 20 percent” or otherwise “within 1 or more than 1 standard deviation”.
The phrase “corresponding to” was removed from all claims in the Reply filed 5/24/2023. The interpretation set forth on record in the Action mailed 2/24/2023 may be reinstated if the phrase is used in subsequent amendments.
The phrases “comprising an amino acid sequence” and “an amino acid sequence corresponding to”, were removed from all claims in the Reply filed 5/24/2023, and replaced with “the” rather than “an”. The difference between “an” and “the” in referring to biopolymers was explained on the record in the Action mailed 2/24/2023.
The term “LHR-A” is understood to refer to the amino acid sequence of 42-489 of SEQ ID NO: 1, and instant SEQ ID NO: 13 (see, e.g., Spec. filed 11/9/2020 at 10 at lines 1-20, page 26 at lines 15-30). “LHR-A” is understood to have the following sequence:
QCNAPEWLPFARPTNLTDEFEFPIGTYLNYECRPGYSGRPFSIICLKNSVWTGAKDRCRRKSCRNPPDPVNGMVHVIKGIQFGSQIKYSCTKGYRLIGSSSATCIISGDTVIWDNETPICDRIPCGLPPTITNGDFISTNRENFHYGSVVTYRCNPGSGGRKVFELVGEPSIYCTSNDDQVGIWSGPAPQCIIPNKCTPPNVENGILVSDNRSLFSLNEVVEFRCQPGFVMKGPRRVKCQALNKWEPELPSCSRVCQPPPDVLHAERTQRDKDNFSPGQEVFYSCEPGYDLRGAASMRCTPQGDWSPAAPTCEVKSCDDFMGQLLNGRVLFPVNLQLGAKVDFVCDEGFQLKGSSASYCVLAGMESLWNSSVPVCEQIFCPSPPVIPNGRHTGKPLEVFPFGKTVNYTCDPHPDRGTSFDLIGESTIRCTSDPQGNGVWSSPAPRCGI
The term “LHR-B” is understood to refer to the amino acid sequence of 490-939 of SEQ ID NO: 1, and instant SEQ ID NO: 14 (see, e.g., Spec. filed 11/9/2020 at 10 at lines 1-20, page 26 at lines 15-30). “LHR-B” is understood to have the following sequence:
LGHCQAPDHFLFAKLKTQTNASDFPIGTSLKYECRPEYYGRPFSITCLDNLVWSSPKDVCKRKSCKTPPDPVNGMVHVITDIQVGSRINYSCTTGHRLIGHSSAECILSGNAAHWSTKPPICQRIPCGLPPTIANGDFISTNRENFHYGSVVTYRCNPGSGGRKVFELVGEPSIYCTSNDDQVGIWSGPAPQCIIPNKCTPPNVENGILVSDNRSLFSLNEVVEFRCQPGFVMKGPRRVKCQALNKWEPELPSCSRVCQPPPDVLHAERTQRDKDNFSPGQEVFYSCEPGYDLRGAASMRCTPQGDWSPAAPTCEVKSCDDFMGQLLNGRVLFPVNLQLGAKVDFVCDEGFQLKGSSASYCVLAGMESLWNSSVPVCEQIFCPSPPVIPNGRHTGKPLEVFPFGKAVNYTCDPHPDRGTSFDLIGESTIRCTSDPQGNGVWSSPAPRCGI
The term “LHR-C” is understood to refer to the amino acid sequence of 940 to 1392 of SEQ ID NO: 1, and instant SEQ ID NO: 15 (see, e.g., Spec. filed 11/9/2020 at 10 at lines 1-20, page 26 at lines 15-30). “LHR-C” is understood to have the following sequence:
LGHCQAPDHFLFAKLKTQTNASDFPIGTSLKYECRPEYYGRPFSITCLDNLVWSSPKDVCKRKSCKTPPDPVNGMVHVITDIQVGSRINYSCTTGHRLIGHSSAECILSGNTAHWSTKPPICQRIPCGLPPTIANGDFISTNRENFHYGSVVTYRCNLGSRGRKVFELVGEPSIYCTSNDDQVGIWSGPAPQCIIPNKCTPPNVENGILVSDNRSLFSLNEVVEFRCQPGFVMKGPRRVKCQALNKWEPELPSCSRVCQPPPEILHGEHTPSHQDNFSPGQEVFYSCEPGYDLRGAASLHCTPQGDWSPEAPRCAVKSCDDFLGQLPHGRVLFPLNLQLGAKVSFVCDEGFRLKGSSVSHCVLVGMRSLWNNSVPVCEHIFCPNPPAILNGRHTGTPSGDIPYGKEISYTCDPHPDRGMTFNLIGESTIRCTSDPHGNGVWSSPAPRCELSVR
The term “LHR-D” is understood to refer to the amino acid sequence of 1393 to 1971 of SEQ ID NO: 1, and instant SEQ ID NO: 16 (see, e.g., Spec. filed 11/9/2020 at 10 at lines 1-20, page 26 at lines 15-30). “LHR-D” is understood to have the following sequence:
AGHCKTPEQFPFASPTIPINDFEFPVGTSLNYECRPGYFGKMFSISCLENLVWSSVEDNCRRKSCGPPPEPFNGMVHINTDTQFGSTVNYSCNEGFRLIGSPSTTCLVSGNNVTWDKKAPICEIISCEPPPTISNGDFYSNNRTSFHNGTVVTYQCHTGPDGEQLFELVGERSIYCTSKDDQVGVWSSPPPRCISTNKCTAPEVENAIRVPGNRSFFSLTEIIRFRCQPGFVMVGSHTVQCQTNGRWGPKLPHCSRVCQPPPEILHGEHTLSHQDNFSPGQEVFYSCEPSYDLRGAASLHCTPQGDWSPEAPRCTVKSCDDFLGQLPHGRVLLPLNLQLGAKVSFVCDEGFRLKGRSASHCVLAGMKALWNSSVPVCEQIFCPNPPAILNGRHTGTPFGDIPYGKEISYACDTHPDRGMTFNLIGESSIRCTSDPQGNGVWSSPAPRCELSVPAACPHPPKIQNGHYIGGHVSLYLPGMTISYICDPGYLLVGKGFIFCTDQGIWSQLDHYCKEVNCSFPLFMNGISKELEMKKVYHYGDYVTLKCEDGYTLEGSPWSQCQADDRWDPPLAKCTSRTHD
As amended 8/07/2025, instant claim 1 is limited to an sCR1 sequence “consisting of” amino acids 42-1392 of instant SEQ ID NO: 1 (i.e., LHR-A, LHR-B, and LHR-C). Examiner notes that the prior art utilizes various nomenclatures to describe the protein of sCR1. Notably, LHR-A, LHR-B, LHR-C, and LHR-D are “long homologous repeats” (“LHRs”), each comprising seven “homologous short consensus repeats” (“SCRs”) (see, e.g., Cohen et al.6 at abs, 2 at 1st full ¶, Fig. 1 on 4, reproduced in part below):
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754
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Accordingly, LHR-A comprises SCRs 1-7; LHR-B comprises SCRs 8-14, LHR-C comprises SCRs15-21; and LHR-D comprises SCRs 22-28. This means that instant SEQ ID NO: 3 consists of SCRs 1-21 of CR1, which is equivalent to consisting of “LHR-A, B, and C” (see, e.g., Cohen at 2 at 1st full ¶, Fig. 1 on 4; see also Spec. filed 11/09/2020 at 10 at lines 1-20).
Additional claim interpretations are set forth below.
Withdrawn Claim Rejections
The rejection of claims 4-5, 7, and 42 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form has been successfully traversed in part by Applicant’s amendments filed 1/27/2026. A revised rejection is set forth below addressing remaining issues applicable to instant claim 42.
New Claim Rejections Necessitated by Applicant Amendment
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 42 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 42 depends from amended claim 1 and attempts to modify the sequence of claim 1 to include post-translational modifications, namely glycans and sialylated residues. Amended claim 1 has been limited to the single sCR1 sequence “wherein the amino acid sequence of the sCR1 variant consists of” amino acids 42-1392 of instant SEQ ID NO: 1, wherein “consists of” excludes any elements, step, or ingredient not specified as present in the sCR1 variant (see, e.g., MPEP § 2111.03(II)). The post-translational modifications are reasonably understood to constitute an “element, step, or ingredient” that is not specified as present at amended claim 1, and SEQ ID NO: 1 does not identify or include sequence positions that may optionally include such modifications (see, e.g., SEQ ID NOs: 1, 3, and 21). Notably, such modification alters the sequences (e.g., glycosidic bonds) and therefore such alterations are reasonably understood to constitute an “element, step, or ingredient” that is not specified as present at amended claim 1. Accordingly, claim 42 is rejected for failing to include all the limitations of the claim upon which it depends.
If supported by the originally filed disclosure, Applicant may address this issue by modifying instant claim 1 to “consist of amino acids 42-1392 of instant SEQ ID NO: 1, wherein the sCR1 variant may optionally comprise glycosylated residues”.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Accordingly, claim 42 is rejected.
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.
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 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.
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 and 42 are rejected under 35 U.S.C. 103 as being unpatentable over US 2012/0232020 (Sept. 13, 2012; cited in previous action)7 and further in view of NCBI NP_000564.28.
Claim Interpretation: The applicable claim interpretation has been set forth above in a separate section, and that discussion is incorporated herein. Amended claim 1 has been limited to the single sCR1 sequence “consisting of” amino acids 42-1392 of instant SEQ ID NO: 1 (i.e., it “consists of” LHR-A, B, and C, which corresponds to SCRs 1-21 of CR1). For purposes of compact prosecution, the limitations of claim 42 have been treated as optionally present and addressed below, but such claim limitations are presently excluded by amended claim 1.
Regarding instant claims 1 and 42, and the general methods of administering a soluble complement receptor type I (sCR1) polypeptide to a subject to prevent or treat a “complement mediated disorder”, US’020 teaches and discloses methods of administering sCR1 polypeptides to patients to “improve organ function” (see, e.g., US’020 at claims 1-4). Regarding claims 1, 42, and the applicable patient population of “subjects”, US’020 identifies that such methods are applicable to any “mammalian” subject, which would include mice, rats, humans, etc. (see, e.g., US’020 at claims 1-4). Regarding claim 1 and the applicable route of administration, US’020 identifies that the disclosed and claimed methods may be performed using a range of administration routes, including intravenous routes (see, e.g., US’020 at claims 1-5; see esp. id. at claim 5). Regarding claims 1 and the applicable dosage, US’020 reasonably directs artisans to utilize dosages that overlap in scope with instant Example 4, including the range of 1-100 mg/kg (see, e.g., US’020 at ¶[0046]). Per MPEP § 2144.05(I), where ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists (see, e.g., MPEP § 2144.05(I)). Accordingly, the dosage utilized in the originally elected species does not distinguish the claimed invention from the cited prior art in a manner that would make the claimed invention unobvious. Regarding claim 1 and an sCR1 fragment “consisting of” LHR-A, B, and C, but lacking LHR-D, US’020 explicitly directs artisans to make and use a fragment of human CR1 comprising
….at least long homologous repeats (LHRs) B and/or C, preferably both LHRs B and C, more preferably long homologous repeats A, B, and C….
(see, e.g., US’020 at ¶[0034]) and explicitly claims embodiments of methods comprising the administration of an sCR1 polypeptide comprising
…a fragment of human CR1 comprising long homologous repeats A, B, and C; . . .
(see, e.g., US’020 at claims 1 and 4). This is pertinent because such sequences correspond to amino acids 42 to 1392 of instant SEQ ID NO: 1 (see, e.g., US’020 at ¶[0034]9, claim 4; compare instant SEQ ID NO: 3 or instant SEQ ID NO: 1 at LHR-A, B, and C with US’020 at SEQ ID NO: 1 at LHR-A, B, and C, noting >99% sequence identity). Accordingly, the structure of a sCR1 fragment comprising LHR-A, B, and C, while lacking LHR-D does not distinguish the claimed invention from the cited prior art in a manner that would make the claimed invention unobvious. Regarding amended claim 1 and the usage of “consisting of” rather than “comprising”, US’020 expressly discloses, claims, and refers to a fragment of human CR1 “comprising” LHRs A, B, and C, but without D (see, e.g., US’020 at ¶[0034], claims 1 and 4). The usage of “comprising” explicitly encompasses “consisting of” within the disclosure of US’020 (see, e.g., US’020 at ¶[0032]), and therefore an artisan would readily appreciate that US’020 directs artisans to human CR1 fragments “consisting of” LHRs A, B, and C, but without D (see, e.g., US’020 at ¶¶[0032], [0034], claims 1 and 4). Although not presently examined, Examiner notes that US’020 provides guidance regarding the use of a sCR1 fragment conjugated to a half-life extending moiety, US’020 identifies that methods of improving in vivo half-life of sCR1 polypeptides was known in the art (see, e.g., US’020 at ¶¶[0029], [0034], claim 4). Specifically, US’020 identifies that it was known in the art that “soluble CR1 polypeptide[s] having modified glycosylation” could be utilized to “improve serum half-life in vivo” (see, e.g., US’020 at ¶¶[0017], [0029], [0034], claim 4). Accordingly, an artisan would readily appreciate that the disclosed methods and disclosed sCR1 polypeptides could be further modified via glycosylation to predictably “improve serum half-life” (see, e.g., US’020 at id.; see esp. id. at ¶[0034]). Regarding claim 42, claim 42 has been rejected under 35 USC § 112(d) above, but is addressed herein to facilitate compact prosecution. To facilitate compact prosecution, claim 42 is reasonably inferred to mean that at least 30% of the total sCR1 variants present are sialylated. Notably, US’020 explicitly details such variants (see, e.g., US’020 at ¶¶[0029]), and expressly claims them (see, e.g., US’020 at claim 4, reciting “a soluble CR1 polypeptide having” glycosylation modified to exhibit “sialyl Lewis X moieties”). Accordingly, such embodiments would be at once envisaged, and an artisan would know how to make, isolate, and purify such sialylated CR1 polypeptides.
US 2012/0232020 differs from the instantly claimed invention as follows: Although US’020 claims methods of administering a sCR1 fragment (glycosylated or not) “consisting of” LHR-A, B, and C a human soluble CR1 polypeptide10, US’020 teaches a sequence sharing only >99% sequence identity to the claimed sequence “consist[ing] of the amino acid sequence of amino acids 42 to 1392 of [instant] SEQ ID NO: 1” rather than 100%.
NP000564.2 is cited herein to establish that other human CR1 sequences were known in the prior art, which LHR-A, B, and C residues with instant SEQ ID NOs: 3 and 21, except with respect to the Histidine tag of SEQ ID NO: 21 (compare instant NP000564.2 with instant SEQ ID NOs: 3 and SEQ ID NO: 1 at positions 42-1392, showing 100% sequence identity).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s):
First, per MPEP § 2144.09(I), a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. Here, the prior art teaches methods of administering an almost identical compound, consisting of LHR-A, B, and C of a human soluble CR1 polypeptide11, to the same or overlapping patient population, via the same intravenous injection route, at the same or overlapping dosage of 1-100 mg/kg, and wherein the compound shares >99% sequence identity with the compound utilized in the claimed method. Accordingly, the prior art teaches methods that appear to be almost identical, have almost identical utilities, and utilize almost identical (>99%) compounds. Accordingly, per MPEP § 2144.09(I), the amended claim scope is rejected as prima facie obvious in view of the primary reference.
In addition, or alternatively, the claimed invention is the simple substitution of one CR1 sequence (i.e., the one taught by US’020) for another CR1 sequence (i.e., NP000564), in the known methods disclosed by US’020 (i.e., using a known compound at a known dosage with a known administration route in a known patient population, with an known predicted and expected outcome), wherein such substitution would yield only predictable results, namely a method of administering a known sCR1 fragment of NP000564 consisting of the respective LHR-A, B, and C of NP000564, at a known dosage, with a known administration route, to a known patient population, to predictably and desirably improve the organ function in subjects exactly as taught and suggested by US’020 (see, e.g., MPEP § 2143(I)(B); see also MPEP § 2144.08(II), noting that both sequences are CR1 proteins and share >99% sequence identity, and therefore would be reasonably understood to be equivalents for applications utilizing CR1 proteins as taught and suggested by the primary reference).
Furthermore, no evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to utilize a known method, with a known compound, at a known dosage, using a known administration route, on a known patient population, to achieve a known result.
Accordingly, claims 1 and 42 are rejected.
Response to Arguments
Applicant's arguments filed 1/27/2026 have been fully considered but not found persuasive as explained below. Arguments addressing canceled claims or withdrawn rejections are moot; remaining applicable arguments are addressed below.
As an initial matter, all of the Examiner’s prior responses remain pertinent and are incorporated into the instant response.
35 USC § 112(d)
Applicant traverses the rejection of claim 42 under 35 USC 112(d) at pages 10-11 (see, e.g., Reply filed 1/27/2026 at 10 at §§ II.C to page 11 at 1st full ¶). The arguments are not found persuasive because they do not reflect the state of the prior art regarding amino acid sequence modification made via post-translational modifications.
It is the Examiner’s understanding that Applicant is alleging that because the “amino acid sequence” of the embodiment at claim 1 “consists of amino acids 42 to 1392 of SEQ ID NO: 1”, that this limitation excludes limitations that “alter the amino acid sequence of amino acids 42 to 1392 of SEQ ID NO: 1” (see, e.g., Reply filed 1/27/2026 at 10-11 at bridging ¶). Examiner concurs with Applicant that that “consisting of” language at claim 1 excludes limitations that “alter the amino acid sequence of amino acids 42 to 1392 of SEQ ID NO: 1”.
However, it is the Examiner’s understanding that Applicant is alleging that post-translational modifications do not “alter the amino acid sequence of amino acids 42 to 1392 of SEQ ID NO: 1”, and are therefore not excluded by the “consists of” limitation of instant claim 1 (see, e.g., Reply filed 1/27/2026 at 10-11 at bridging ¶). Examiner disagrees for the following reasons:
First, per the MPEP, “consisting of” excludes any elements, step, or ingredient not specified (see, e.g., MPEP § 2111.03(II)). This means that claim 1 requires the exact structure corresponding to the amino acid sequence of amino acids 42 to 1392 of SEQ ID NO: 1 (see instant claim 1).
Second, post-translational modifications literally and inherently alter the exact, covalent structure of an amino acid by changing both the physical structure and covalent bonds of and amino acid, and such structural alterations also alter the biochemical properties of the amino acid12. Therefore, a post-translational modification would, in fact, literally and inherently alter the covalent structure and properties of the that amino acid sequence corresponding to amino acids 42 to 1392 of SEQ ID NO: 1.
Third, post-translational modifications are recognized in the prior art to correspond to distinct structures and functionality, which require different methods of manufacture13 and different methods of sequence alignment and discovery14. Accordingly, the prior art supports a conclusion that an amino acid sequence that “consists of amino acids 42 to 1392 of SEQ ID NO: 1” would not be practically considered by an artisan to have the exact structure corresponding to the amino acid sequence of amino acids 42 to 1392 of SEQ ID NO: 1 (see, e.g., MPEP § 2111.03(II)).
Fourth, it is the Examiner’s understanding that Applicant relies upon a single quote from Rademacher for their position (see, e.g., Reply filed 1/27/2026 at 10-11 at bridging ¶), but this reliance is misplaced because the quote does not reflect or rely upon the legal meaning of “consists of” as used in patent prosecution. Rather, at best, this quote represents “comprising” or “consisting essentially of” language, recognizing that a sequence may further comprise different post-translational modifications (see id).
Fifth, N- or O-linked glycosylation does in fact alter the underlying chemical structure of amino acids. For example, N-linked Asn and Asn have non-identical chemical structures, covalent bonds, molecular weights, and chemical properties. as id above in view of Sirota, Gupta, and Chen. If Applicant continues to disagree, Applicant should provide a side-by-side chemical structure of the unmodified and modified amino acids, and explain how the different chemical structures are identical.
In sum, Applicant’s position is not persuasive because sequences that are covalently modified are not, in fact, chemically, physically, or practically identical to sequences lacking covalent modifications. Therefore, the rejection is maintained because “consists of” language excludes any elements, step, or ingredient not specified (see, e.g., MPEP § 2111.03(II)), which means that claim 1 requires the exact, unmodified structure corresponding to the amino acid sequence of amino acids 42 to 1392 of SEQ ID NO: 1 (see instant claim 1), and therefore excludes covalent modifications (PTMs) that alter the covalent bonds and structure of the required sequence.
Applicant is advised that they may review MPEP § 2111.03 for alternative transitional phrases that more accurately capture the intended claim scope (e.g., potentially “comprising” or “consisting essentially of”).
Accordingly, the rejection is maintained.
35 USC § 103
Applicant traverses the rejection of claims 1 and 42 under 35 USC 103 at pages 11-1 (see, e.g., Reply filed 1/27/2026 at 11 at § III to page 19 at 2nd full ¶). These arguments have been addressed below.
Examiner’s prior responses remain applicable: Examiner notes that multiple arguments appear to be raised again, but were previously considered and not found persuasive for reasons for record (see, e.g., Action mailed 8/27/2025 at 20-24). The Examiner’s prior response has been reviewed and deemed applicable, and is therefore incorporated into the instant response.
Summary of the Primary reference: The prior art of US’020 claims methods of administering prior art compounds to a prior art patient population, and such claims were subsequently patented (see, e.g., US 9649356 B2 at claims 1-5, essentially verbatim to claims 1-5 of US’020). The primary reference directed artisans to use one of only two “more” preferred compounds, of which one is recited at instant claim 1 (see, e.g., US’020 at ¶[0034], stating “more preferably long homologous repeats A, B, and C or A, B, C, and D….”). The prior art further directed artisans to practice the prior art methods using known dosages (see, e.g., US’020 at ¶[0046]) and administration routes (see, e.g., US’020 at ¶[0046]), wherein the primary reference provides a predicted and expected result, namely administering such compounds to such patients at such concentrations via such administration routes would be predicted and expected to “inhibit systemic and/or local complement activation of a soluble complement receptor type I (sCRl) polypeptide” (see, e.g., US’020 at claims 1-5).
Assertion of unexpected results: It is the Examiner’s understanding that Applicant again alleges the existence of unexpected results sufficient to rebut a determination of prima facie obviousness commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 (see, e.g., Reply filed 1/27/2026 at 12 at §§III.A to 17 at final ¶; see also Reply filed 8/07/2025 at 11-12 at bridging ¶, 12-13 at bridging ¶, Table 1; see also Reply filed 1/28/2025 at 11-12 at bridging ¶ to 13 at 1st full ¶, previously alleging unexpected results on the same evidence). It is the Examiner’s understanding that the basis for the allegation of unexpected results depends upon the Declaration filed 1/27/2026 (see, e.g., Reply filed 1/27/2026 at 12 at §§III.A to 17 at final ¶, citing the Declaration). Accordingly, these arguments have been considered and not found persuasive in view of the Declaration, which is addressed in a separate section below, but not repeated here. In brief, the proffered data is insufficient to establish unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02, and rebut prima facie obviousness when weighed against the prior art of record.
Allegation of improper hindsight bias: It is the Examiner’s understanding that Applicant is again alleging that the Examiner’s conclusion of prima facie obviousness is based upon “impermissible hindsight” (see, e.g., Reply filed 1/27/2026 at 18 at §§III.B to 19 at 2nd full ¶; see also Reply filed 1/22/2024 at 13 at 1st partial ¶). In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the instant case, oddly the basis for Applicant’s allegation of impermissible hindsight appears to involve the Applicant admitting that the prior art does, in fact, explicitly teach “a fragment of human CR1 comprising long homologous repeats A, B and C” (see, e.g., Reply filed 1/27/2026 at 18 at 1st and 2nd full ¶¶). Accordingly, Applicant fails to identify any guidance derived from the instant disclosure required to arrive at “a fragment of human CR1 comprising long homologous repeats A, B and C”. Accordingly, no evidence of improper hindsight bias has been shown because, as acknowledged by the Applicant, the art does in fact teach the limitations at issue.
No impermissible “picking and choosing” required to arrive at the claimed invention: It is the Examiner’s understanding that Applicant is again alleging that the Examiner’s conclusion of prima facie obviousness is based upon “impermissible hindsight”, based upon the allegation that the structure at issue is “one of a very large number of human CR1 variants” (see, e.g., Reply filed 1/27/2026 at 18 at §§III.B to 19 at 2nd full ¶; see also Reply filed 1/22/2024 at 13 at 1st partial ¶). Examiner again directs Applicant to the claims of US 2012/0232020, wherein US’020 expressly claims methods of administering to subjects a “soluble complement receptor type I (sCR1) polypeptide” selected from a group of fifteen fragments, including “a fragment of human CR1 comprising long homologous repeats A, B, and C” (see, e.g., US’020 at claims 1-5), wherein such fragment is identified as one of only two “more” preferable sequences (see, e.g., US’020 at ¶[0034]). Absent objective evidence to the contrary, prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), which includes the expressly claimed inventions of US’020, which were subsequently patented (see, e.g., US 9649356 B2 at claims 1-4, essentially verbatim to claims 1-4 of US’020). Accordingly, the record shows that the prior art was found to satisfy the requirements of 35 USC §§101, 112, 102, and 103. Regarding “picking and choosing” allegations, the courts have repeatedly identified that the disclosure of one embodiment does not constitute a “teaching away” from another embodiment (see, e.g., MPEP § 2123(II); see also Merck & Co. v. Biocraft Labs, Inc., 874 F .2d 804,807 (Fed. Cir. 1989), noting "That the '813 patent discloses a multitude of effective combinations does not render any particular formulation less obvious. This is especially true because the claimed composition is used for the identical purpose."). Here, as evidenced by claims 1-4 of US’020 (i.e., corresponding to US’356 at claims 1-4), the prior art is presumed fully enabled for using any of the enumerated fragments in the explicitly recited claims, wherein the “a fragment of human CR1 comprising long homologous repeats A, B, and C” would be readily selected as it is one of only two “more” preferable sequences (see, e.g., US’020 at claims 1-5, ¶[0034]).
Suggestions regarding the existence of skepticism of experts or inoperability of the prior art: Upon review of the Applicant’s arguments (see, e.g., Reply filed 1/27/2026 at 11 at § III to page 19 at 2nd full ¶), Examiner notes the existence of multiple conclusory statements, statements suggesting the existence of skepticism of experts, or statements suggesting that the full scope of the prior art of US’020 (corresponding to issued US’356) is not fully enabling or operable (see, e.g., Reply filed 1/27/2026 at 11 at § III to page 19 at 2nd full ¶). If Applicant means to suggest the existence of skepticism of experts, such evidence should be filed per MPEP § 716.05 as evidence is required to establish skepticism of experts. If Applicant means to suggest that the prior art is inoperable, such evidence should be filed per MPEP § 716.07 as evidence is required to establish skepticism of experts. In the absence of such evidence, such statements are understood to be unsupported conjecture of counsel, which cannot take the place of factually supported objective evidence on record (see, e.g., In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). Here, the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)), and no objective evidence rebutting this presumption has been placed on record to date. If Applicant means to reference and rely upon statements made in the Declaration filed 1/27/2026, Examiner notes that this Declaration has been considered in a separate section below, but found insufficient to rebut prima facie obviousness or to otherwise establish the existence of unexpected results.
Suggestions that performing the prior art method using prior art compounds at prior art dosages administered via prior art administration routes would would lead to previously unappreciated results do not weigh in favor of a determination of obviousness: It is the Examiner’s understanding that Applicant alleges that the instant Inventor’s have discovered that following the guidance of the prior art and administering a prior art compound to the same patient population at the same dosage via the same administration route yields benefits that were not previously appreciated in the prior art (see, e.g., Reply filed 1/27/2026 at 12 at §§III.A to 17 at final ¶). In response to applicant's argument that the claimed invention shows benefits not contemplated by the prior art, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Here, the pending claims read upon the prior art method of administering the same compound, to the same or overlapping patient population, at the same or overlapping dosage, via the same or overlapping routes of administration, to achieve a different result (see, e.g., US’020 at claims 1-5; see also US 9649356 B2 at claims 1-5, which is an issued patent reciting, essentially verbatim, claims 1-5 of US’020). Accordingly, simply following the exact guidance of the prior art, such benefits would have necessarily occurred unless the full scope of the instant claims are not fully enabled.
Applicant has a different rationale for administering the prior art compounds to a prior art patient population at a prior art dosage via a prior art administration route than relied upon by the Examiner: Upon review of the Applicant’s arguments, it is the Examiner’s understanding that the Applicant has a different rationale for arriving at the instantly claimed invention of administering the same compound to the same patient population at the same dosage and via the same route of administration than relied upon by the Examiner (see, e.g., Reply filed 1/27/2026 at 12 at §§III.A to 19 at 2nd full ¶). Per MPEP § 2144(IV), it is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006). Here, the rationale supporting the Examiner’s conclusion of prima facie obviousness is explicitly set forth in the rejection (i.e., MPEP § 2144.09(I), MPEP § 2143(I)(B), and MPEP § 2144.08(II)). Accordingly, the mere fact that Applicant relied upon a different rationale than the Examiner is insufficient to rebut prima facie obviousness.
Allegations that a first prior art compound lacks the efficacy of a different prior art compound, when used within prior art methods, does not render the prior art teachings regarding the first compound inapplicable: Upon review of the Applicant’s arguments (see, e.g., Reply filed 1/27/2026 at 12 at §§III.A to 17 at final ¶), it is the Examiner’s understanding that Applicant is alleging that one prior art compound is superior to a second prior art compound (see id). This line of arguments is not persuasive as follows: First, the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Second, the teachings of preferred embodiments do not constitute a teaching away from other disclosed embodiments (see, e.g., MPEP §§ 2123(II)). Third, “conclusive proof of efficacy is not required to show a reasonable expectation of success” (see, e.g., MPEP §§ 2143.02(I)). Fourth, “Obviousness does not require absolute predictability, but at least some degree of predictability is required” (see, e.g., MPEP §§ 2143.02(II)), and here “some degree of predictability” is satisfied upon the assumption that the prior art is enabled to achieve exactly what is claimed (see, e.g., US’020 at claims 1-5; see also US 9649356 B2 at claims 1-5, which is an issued patent reciting, essentially verbatim, claims 1-5 of US’020). Fifth, allegations of additional or latent properties of a prior art element not recognized in the prior art is explicitly addressed at MPEP § 2145(II), which explains that “Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979)”. In sum, Arguments of efficacy, while germane to arguments attempting to rebut prima facie obviousness under MPEP 716.02, are not persuasive to rebut a determination of prima facie obviousness in view of the instant facts.
Therefore, all arguments raised by the Applicant have been fully considered but not found persuasive. Therefore, the rejection is maintained.
Response to Declaration under 37 C.F.R. §1.132 by Matthew Hardy
The affidavit under 37 CFR 1.132 filed 1/27/2026 is insufficient to overcome the rejections of claims 1 and 42 as set forth in the instant Office action. A detailed explanation of why the affidavit or declaration is insufficient is provided below. The legal standards of review and consideration of Declaration under 37 C.F.R. §1.132 are discussed at MPEP § 716.01.
Interest of the Expert in the Outcome of the Case
Per MPEP 716.01(c)(III), in assessing the probative value of an expert opinion, the examiner must consider the interest of the expert in the outcome of the case. Ashland Oil, Inc. v. Delta Resins & Refractories, Inc., 776 F.2d 281, 227 USPQ 657 (Fed. Cir. 1985), cert. denied, 475 U.S. 1017 (1986). Here, the Declarant is a named inventor and therefore has a clear interest in the outcome of the case.
Nature of the Matter Sought to be Established
Per MPEP 716.01(c)(III), in assessing the probative value of an expert opinion, the examiner must consider the nature of the matter sought to be established. Ashland Oil, Inc., 776 F.2d 281. Here, the Declarant is attempting to establish (i) that examined failed to establish prima facie obviousness (see, e.g., Dec. filed 1/27/2026 at ¶¶5, 7-12, 28), and (ii) the existence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 (see, e.g., Dec. filed 1/27/2026 at ¶¶6-7, 13-28).
Opinions as to Legal Conclusions
Per MPEP 716.01(c)(III), any opinions expressed by Declarant regarding legal conclusions are not entitled to any weight; however, if present, the underlying basis for any opinion as to legal conclusions has been fully considered as detailed below.
Per MPEP § 716.01(c)(III), an affidavit or declaration which states only conclusions may have some probative value, such an affidavit or declaration may have little weight when considered in light of all the evidence of record in the application (see, e.g., In re Brandstadter, 484 F.2d 1395, 179 USPQ 286 (CCPA 1973); see also Ex parte Gray, 10 USPQ2d 1922 (Bd. Pat. App. & Inter. 1989).
Accordingly, statements pertaining to the legal conclusions are acknowledged, but not entitled to any weight, but the underlying basis and supporting evidence underlying such opinions have been fully considered below consistent with the guidance of the MPEP.
Presence or absence of factual support for the expert’s opinion
Per MPEP 716.01(c)(III), in assessing the probative value of an expert opinion, the examiner must consider the presence or absence of factual support for the expert’s opinion. Ashland Oil, Inc., 776 F.2d 281.
Prima facie Obviousness
Arguments alleging a lack of prima facie obviousness are set forth in the Declaration (see, e.g., Dec. filed 1/27/2026 at ¶¶5, 7-12, 28), and the evidence supporting these allegations is considered below.
Undisputed issues: It is the Examiner’s understanding that Declarant does not dispute that the prior art of US’020 literally claims methods of administering prior art compounds to a prior art patient population, and such claims were subsequently patented (see, e.g., US’020 at claims 1-5; see also US 9649356 B2 at claims 1-5, essentially verbatim to claims 1-5 of US’020). It is the Examiner’s understanding that Declarant does not dispute that the primary reference directed artisans to use one of only two “more” preferred compounds, of which one is recited at instant claim 1 (see, e.g., US’020 at ¶[0034], stating “more preferably long homologous repeats A, B, and C or A, B, C, and D….”). It is the Examiner’s understanding that the Declarant does not dispute that the prior art literally directs artisans to practice the prior art methods using known dosages (see, e.g., US’020 at ¶[0046]) and known administration routes (see, e.g., US’020 at ¶[0046]), wherein such methods yield predicted and expected result, namely that administering such compounds to such patients at such concentrations via such administration routes would be predicted and expected to “inhibit systemic and/or local complement activation of a soluble complement receptor type I (sCRl) polypeptide” (see, e.g., US’020 at claims 1-5).
Allegation of lack of motivation to combine is not persuasive: It is the Examiner’s understanding that Applicant is alleging a lack of motivation to combine (see, e.g., Dec. filed 1/27/2026 at ¶¶5, 7-12, 28). In response, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, the rationale supporting the Examiner’s conclusion of prima facie obviousness is explicitly set forth in the rejection (i.e., MPEP § 2144.09(I), MPEP § 2143(I)(B), and MPEP § 2144.08(II)). Accordingly, the Examiner has expressly set forth on record multiple rationales supporting a conclusion of prima facie obviousness, and Declarant fails to identify how the elements of such rationales have not been fully satisfied. Accordingly, argument alleging a lack of motivation to combine are not persuasive.
The prior art is presumed fully enabled for all that it discloses, and the existence of disclosed examples and preferred embodiments do not constitute a teaching away: It is the Examiner’s understanding that Applicant is alleging a lack of motivation to combine (see, e.g., Dec. filed 1/27/2026 at ¶¶5, 7-12, 28), presumably because US’020 taught a “most preferred embodiment” (see, e.g., Dec. filed 1/27/2026 at ¶9). This is not persuasive for reasons of record:
First, the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), and this presumption has not been rebutted with evidence commensurate in scope with MPEP § 716.07.
Second, the teachings of preferred embodiments do not constitute a teaching away from other disclosed embodiments (see, e.g., MPEP §§ 2123(II)). Here, it is undisputed that the prior art literally, implicitly, inherently, and explicitly claims and discloses methods of administering one of only two “more” preferred compounds (see, e.g., US’020 at claims 1-5, ¶[0034], stating “more preferably long homologous repeats A, B, and C or A, B, C, and D….”), wherein the primary reference directs artisans to perform such methods using known dosages (see, e.g., US’020 at claims 1-5, ¶[0046]) and known administration routes (see, e.g., US’020 at claims 1-5, ¶[0046]), wherein such methods yield predicted and expected results in view of the prior art, namely administering such compounds to such patients at such concentrations via such administration routes would be predicted and expected to “inhibit systemic and/or local complement activation of a soluble complement receptor type I (sCRl) polypeptide” exactly as taught and disclosed by the prior art (see, e.g., US’020 at claims 1-5).
Accordingly, all arguments alleging or suggesting that somehow an artisan would dismiss, ignore, or otherwise pretend that entire claims and portions of the US’020 did not exist, simply because US’020 identified a different “most preferred” embodiment, are not persuasive.
Arguments alleging lack of reasonable expectation of success based upon post-filed art: It is the Examiner’s understanding that Declarant is alleging a lack of motivation to combine (see, e.g., Dec. filed 1/27/2026 at ¶¶5, 7-12, 28), presumably at least in part because of the post-filed references of Hardy2023 and Hardy2022 (see, e.g., Dec. filed 1/27/2026 at ¶8). This line of reasoning is not persuasive because Hardy2023 and Hardy2022 were published after the instant Application was filed, and the determination of obviousness and reasonable expectation of success is determined before the effective filing date of the claimed invention (see, e.g., MPEP § 2143.02(III)). Accordingly, reliance upon such post-filed art is analogous to improper hindsight reasoning; therefore, arguments alleging lack of reasonable expectation of success based upon post-filed art is not persuasive.
Arguments alleging lack of reasonable expectation of success based upon other references: It is the Examiner’s understanding that Declarant is alleging a lack of motivation to combine (see, e.g., Dec. filed 1/27/2026 at ¶¶5, 7-12, 28), presumably at least in part because art not relied upon by the Examiner (e.g., Tas, Jacquet, Hardy2022, Hardy2023) (i) constituted a “teaching away” from the claimed invention (see, e.g., Dec. filed 1/27/2026 at ¶8); (ii) allegedly would suggest to an artisan that embodiments lacking LHR-D were inoperative (see, e.g., Dec. filed 1/27/2026 at ¶8), or (iii) allegedly would suggest to an artisan that embodiments lacking LHR-D had reduced potency and efficacy (see, e.g., Dec. filed 1/27/2026 at ¶8; see also id. at ¶11). This is not persuasive for the following reasons:
First, none of cited art references at issue “teach away” from the claimed invention since they do not actually “criticize, discredit, or otherwise discourage the solution claimed” (see, e.g., MPEP § 2141.02(VI)), and Declarant has not identified any disclosure that “criticizes, discredits, or otherwise discourages the solution claimed”. Accordingly, no “teaching away” has been identified on record.
Second, the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), and none of the prior art references cited actually provide any credible evidence that embodiments lacking LHR-D were inoperative or that the instant claims distinguish from the prior art, as required to establish inoperability per MPEP § 716.07. Accordingly, the full scope of US’020 at claims 1-5 are presumed fully enabled and operable.
Third, at best, the prior art suggests that embodiments lacking LHR-D might have reduced potency and efficacy compared to the full-length sCR1 (see, e.g., Dec. filed 1/27/2026 at ¶8). However, this is consistent with the teachings of US’020, which identifies that LHR-ABC one of only two “more” preferred compounds (see, e.g., US’020 at claims 1-5, ¶[0034], but that LHR-ABCD is the most preferred compound. Critically, “conclusive proof of efficacy is not required to show a reasonable expectation of success” (see, e.g., MPEP §§ 2143.02(I)), and “obviousness does not require absolute predictability, but at least some degree of predictability is required” (see, e.g., MPEP §§ 2143.02(II)).
Accordingly, the cited art references do not “teach away” from the solutions explicitly and expressly claimed by US’020, or otherwise establish that such embodiments are not operable and fully enabled (see, e.g., MPEP § 716.07).
Declarant appears to have a different rationale for administering the prior art compounds to a prior art patient population at a prior art dosage via a prior art administration route than relied upon by the Examiner: Upon review of the Declarant’s arguments, it is the Examiner’s understanding that the Applicant has a different rationale for arriving at the instantly claimed invention of administering the same compound to the same patient population at the same dosage and via the same route of administration than relied upon by the Examiner (see, e.g., (see, e.g., Dec. filed 1/27/2026 at ¶¶5, 7-12, 28; see also Reply filed 1/27/2026 at 12 at §§III.A to 19 at 2nd full ¶). Per MPEP § 2144(IV), it is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006). Here, the rationale supporting the Examiner’s conclusion of prima facie obviousness is explicitly set forth in the rejection (i.e., MPEP § 2144.09(I), MPEP § 2143(I)(B), and MPEP § 2144.08(II)). Accordingly, the mere fact that Declarant has relied upon a different rationale than the Examiner is insufficient to rebut prima facie obviousness.
Declarant appears to allege that administering a prior art element to a prior art patient population via a prior art administration route and prior art dosage would yield previously unappreciated, latent properties: It is the Examiner’s understanding that Applicant is alleging that a prima facie case of obviousness was not established because the prior art did not teach the alleged additional or latent properties disclosed in the instant Application (see, e.g., Dec. filed 1/27/2026 at ¶¶5, 7-12, 28). Declarant is directed to MPEP § 2145(II), which explains that “Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA). The fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Accordingly, such arguments, while germane to arguments attempting to rebut prima facie obviousness under MPEP 716.02, are not persuasive to rebut a determination of prima facie obviousness in view of the instant facts.
Declarant alleges that an artisan would lack motivation to select an explicitly taught and disclosed prior art element for the use it is explicitly taught for in the prior art: Declarant alleges that “a POSA would not have been motivated to pick the claimed sCR1 variant” because of the “functional importance of LHR-D” (see, e.g., Dec. filed 1/27/2026 at ¶¶10). This conclusory statement is directly contradicted by the prior art of US’020 and its claims (see, e.g., US’020 at claims 1-5; see also US 9649356 B2 at claims 1-5, essentially verbatim to claims 1-5 of US’020). Here, there is a reasonable expectation of success because the prior art explicitly and expressly teaches the administration of the compound to patients, and the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Accordingly, arguments amounting to an argument that an artisan would dismiss or ignore the teachings of the prior art, in the absence of evidence of inoperability, are not persuasive.
Declarant alleges that an artisan would not have had a reasonable expectation of successfully using a prior art compound in a method that it is explicitly taught for use in, wherein the prior art expressly discloses a predicted and expected result: It is the Examiner’s understanding that Declarant alleges that that there would not be a reasonable expectation of successfully utilizing the prior art compound of US’020 (e.g., LHR-ABC) in the explicitly recited and claimed methods of US’020, because US’020 only exemplifies methods utilizing LHR-ABCD, and that LHR-ABCD is the “most preferred” embodiment (see, e.g., Dec. filed 1/27/2026 at ¶¶9, 11-12). This is not persuasive because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). As noted above, the teachings of preferred embodiments do not constitute a teaching away from other disclosed embodiments (see, e.g., MPEP §§ 2123(II)), and “conclusive proof of efficacy is not required to show a reasonable expectation of success” (see, e.g., MPEP §§ 2143.02(I)). In addition, Examiner notes that “Obviousness does not require absolute predictability, but at least some degree of predictability is required” (see, e.g., MPEP §§ 2143.02(II)), and here “some degree of predictability” is satisfied upon the assumption that the prior art is enabled to achieve exactly what is claimed (see, e.g., US’020 at claims 1-5; see also US 9649356 B2 at claims 1-5, which is an issued patent reciting, essentially verbatim, claims 1-5 of US’020). Accordingly, Declarant fails to credibly explain exactly why, in view of US’020, an artisan would not predict and expect that administering LHR-ABC to a patient exactly as claimed would not yield the exact results taught and claimed by US’020 (see, e.g., US’020 at claims 1-5; see also US 9649356 B2 at claims 1-5, which is an issued patent reciting, essentially verbatim, claims 1-5 of US’020). Accordingly, arguments amounting to an allegation that artisans would simply ignore or dismiss the express teachings of the prior art, are not persuasive.
Accordingly, all arguments raised and directed to establishing that the Examiner failed to establish prima facie obviousness have been fully considered but not found persuasive.
Allegations of Unexpected Results
Arguments alleging the existence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 (see, e.g., Dec. filed 1/27/2026 at ¶¶6-7, 13-28) have been fully considered, but not found persuasive for the following reasons.
The basis for the allegation of unexpected results is understood to be premised upon the data of Wymann and Bongoni (see, e.g., Dec. filed 1/27/2026 at 13-28). This data have been fully considered but not found sufficient to evidence unexpected or superior results as required by MPEP § 716.02 for the reasons discussed below.
Neither Wymann or Bongoini provide a comparison of the “claimed invention” with the closest prior art of record: MPEP § 716.02 requires a comparison of the closest existing prior art with the “claimed invention” (see, e.g., MPEP § 716.02(b)(III), § 716.02(d), 716.02(e)(I), passim). Here, the claimed invention is an in vivo method of administering a sCR1 variant to a subject, wherein the amino acid sequence of the sCR1 variant consists of the amino acid sequence of amino acids 42 to 1392 of SEQ ID NO: 1 (see, e.g., instant claim 1). However, Wymann and Bongoni identify that the tested compounds did not “consist of amino acids 42 to 1392 of SEQ ID NO: 1” as required by instant claim 1, but instead that the tested compounds were ill-defined “sialylated entities” having unknown modifications at unknown positions (see, e.g., Wymann at 11 at col II; see, e.g., Bongoni at 2 at 1st full ¶). Accordingly, as an initial matter, neither Wymann nor Bongoni satisfy the requirements of MPEP § 716.02, because they fail to provide a comparison of the “claimed invention” as actually claimed (see, e.g., MPEP § 716.02(b)(III), § 716.02(d), 716.02(e)(I), passim).
In the alternative, even assuming arguendo that “consisting of” language was subsequently deemed to permit covalent modifications at positions 42-1392 of SEQ ID NO: 1, this would simply raise issues under MPEP 716.02(d). This is because there are over 300 different types of post-translational modifications15, and if claim 1 permits such scope, then the tested compounds are not commensurate in scope with the claimed invention since such modifications substantially alter biophysical properties of sequences16, and even render sequences inoperative due to improper folding17. Accordingly, even if the disclosed tests were deemed to be directed to the “claimed invention”, it would alternatively mean that the proffered data was insufficient to establish unexpected results under MPEP 716.02(d), as no PTMs other than sialylation at unspecified positions was tested or disclosed, and the proffered data shows that even the limited sialylation tested altered the properties of the disclosed compounds (see, e.g., Wymann at Table 4 at page 9).
Neither Wymann nor Bongoni satisfy the requirements of MPEP § 716.02(d): MPEP § 716.02(d) requires proffered data to be commensurate in scope with the claimed invention. Here, the instant claims are not limited by subject, administration route, dosage concentration, dosage frequency, or by timing of administration (see, e.g., instant claim 1). However, Wymann nor Bongoni are limited to highly specific subjects (mice), particular routes of administration, particular dosage concentrations, timing, temperature, etc. (see, e.g., Bongoni at Fig. 2, 8-9 at methods; see, e.g., Wymann at Table 4, Fig. 6, Fig. 7). No data showing that such results can be extrapolated to the full scope of instant claim 1 has been placed on record at this time (see, e.g., MPEP § 716.02(d)).
It is the Examiner’s understanding that Applicant attempts to rely upon in vitro data (see, e.g., Dec. at ¶¶19-20, referring to Wymann at Table 1). A showing commensurate in scope with the requirements of MPEP § 716.02 requires a comparison of the “claimed invention” (see, e.g., MPEP § 716.02(b)(III), § 716.02(d), 716.02(e)(I), passim). Here, the claimed invention is “a method of inhibiting complement activity in a subject, the method comprising administering a [sCR1] variant to the subject, wherein the amino acid sequence of the sCR1 variant consists of the amino acid sequence of amino acids 42 to 1392 of SEQ ID NO: 1 (see, e.g., instant claim 1). Accordingly, the claims recite and require an in vivo method. Accordingly, in vitro data does not illustrate the claimed method as required by MPEP § 716.02.
It is the Examiner’s understanding that Applicant alleges that they would have “reasonably expected similar superior inhibitory activity” from conjugates, although none were tested and zero data pertaining to conjugates was actually provided (see, e.g., Dec. at ¶¶21, 26). Examination has not been extended to conjugates at this time, but Examiner notes that zero evidence of record shows that any proffered data could be meaningfully extended to all possible conjugates as presently claimed. Accordingly, such opinions in the absence of evidence do not satisfy the requirements of MPEP § 716.02(b)(I)-(II), which identifies that the burden is on the Applicant to establish results are unexpected and significant.
Examiner notes that the closest existing prior art is Example 1 of US’020 (see, e.g., US’020 starting at ¶[0055]), wherein Group 2 and Group 3 are equally close (see, e.g., US’020 starting at ¶[0060]-[0061]; see, e.g., MPEP 716.02(e)(II), noting situations with equally close prior art).
The practical significance of the proffered data is unclear: Per MPEP § 716.02(b)(I)-(II), the burden is on the Declarant to fully explain any proffered data, wherein the evidence relied upon should establish "that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance." This is because the claimed invention is directed to an unmodified sequence with no PTMs, consisting of only positions 42 to 1392 of instant SEQ ID NO: 1, but no evidence or explanation of how such proffered data applies to sequences lacking post-translational modifications has been set forth by Applicant. Furthermore, the art teaches that PTMs substantially and materially impact the physical and chemical properties of proteins18, 19, 20, and no guidance is provided permitting artisans to extrapolate the limited, ill-defined data pertaining to highly or lowly sialylated compounds to completely unmodified sequences. Accordingly, the practical significance of the proffered data as it relates to the claimed invention (or other variants having one of 300+ other PTMs) is unknown and the Declarant fails to address this issue.
Per MPEP § 716.02(c), the evidence of unexpected and expected results must be weighed. Here, the prior art of record establishes that the prior art contains multiple documents guiding and directing artisans to methods of making and utilizing sCR1 polypeptides lacking LHR-D21, and the claims of US’020 have even issued (i.e., corresponding to US’356 at claims). In view of the prior art of record, an artisan would readily make and use sCR1 polypeptides consisting of LHR-ABC, administer such compounds to patients at known concentrations via known administration routes, wherein such methods would predictably and expectedly achieve the exact outcomes claimed, namely they would “inhibit systemic and/or local complement activation of a soluble complement receptor type I (sCRl) polypeptide” (see, e.g., US’020 at claims 1-5; see also US’356 at claims 1-5). The proffered data, at best, suggests that there may exist an improvement in such methods when using the “more” preferred compound of the prior art rather than the “most” preferred compound. Upon weighing the evidence of record, such a result, even when viewed in the light most favorable to the Declarant, cannot be said to rebut the substantial evidence supporting obviousness (see, e.g., MPEP § 716.02(c)). Accordingly, the proffered evidence under MPEP § 716.02 has been fully considered and weighed, but not found sufficient to rebut prima facie obviousness in view of the prior art, which expressly teaches methods of administering compounds comprising LHR-ABC to patients to achieve a known, expected, and predicted outcome.
Weighing Objective Evidence
Per MPEP § 716.01(d), the ultimate determination of patentability must be based on consideration of the entire record and notes that submission of evidence of patentability does not mandate a conclusion of patentability in and of itself. Here, no showing of unexpected results between the claimed invention and the closest prior art of record has been set forth for the reasons discussed above. Therefore, in view of the record as a whole, the Declaration is insufficient to overcome the rejections of record. Even assuming arguendo that the proffered data was considered equivalent to the claimed invention, it would not outweigh the substantial evidence of obviousness currently of record22, because the prior art literally and explicitly guides artisans to make use the compound claimed in the methods as claimed, and directs artisans to utilize overlapping concentration and administration routes. The proffered data, at best, suggests that there may exist an improvement in such methods when using the “more” preferred compound of the prior art rather than the “most” preferred compound, but such improvement does not negate that the prior art literally taught and directed artisans to utilize the same compound within the same patient population at the same dosage via the same administration route to achieve the results taught and acknowledged by the prior art (see discussion above, see rejection above).
Accordingly, the rejections are maintained.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US 5,472,939 (cited in previous action) claims methods of treating or preventing damage in patients caused by inflammation comprising administering to the patient a CR1 molecule encoded by PT-CR1c1 or pT-CR1c5 (see, e.g., US’939 at claims 21, 24-25); wherein in view of Figure 20 of US’939, it is understood that the encoded proteins comprise LHR-A, but lack a complete LHR-D (see, e.g., US’939 at claims 21, 24-25, and Figure 20).
US 5,456,909 (cited in previous action) teaches and discloses glycosylated forms of sCR1 having extended half-lives in vivo (see, e.g., US’909 at title, abs, passim).
US 2015/0079084 A1 (Mar. 19, 2015, cited in previous action) teaches fusion proteins that comprise a “complement inhibiting domain” (“CID”) (see, e.g., US’084 at ¶¶[0009], [0049]-[0055]), which may comprise “homologous short consensus repeats” (“SCRs”) of 1-21 (see, e.g., id.; see id. esp. at ¶[0051]). As noted in the claim interpretation section in view of Cohen (see, e.g., Cohen at abs, 2 at 1st full ¶, Fig. 1 on 4), LHR-A comprises SCRs 1-7; LHR-B comprises SCRs 8-14, LHR-C comprises SCRs15-21; and LHR-D comprises SCRs 22-28. Accordingly, US’084 reasonably teaches and discloses compounds comprising SCRs 1-21 of CR1, which is equivalent to comprising “LHR-A, B, and C” (see, e.g., US’084 at ¶[0051]).
US 2017/0020926 A1 (Jan. 26, 2017; cited in previous action) teaches and disclosed CR1 polypeptides comprising one or more SCRs of CR1, or one or more LHRs, but less than all SCRs or LHRs (see, e.g., US’926 at ¶[0267])
WO 2012/058479 (May 3, 2012; cited in IDS filed 11/09/2020) teaches and discloses material essentially identical in scope to US 2012/0232020 (Sept. 13, 2012), as discussed above.
Terpe23 establishes that polyhistidine tags are well-known and understood in the protein arts (see, e.g., Terpe at title, abs, Tables 1-2 on 524), and identifies that affinity-tags are used to facilitate purification of recombinant polypeptides (see, e.g., Terpe at 523 at col I-II at § Introduction).
US 6057131 (May 2, 2000; cited in previous action) pertains the preparation and use of sialylated glycoforms of sCR1 (see, e.g., US’131 at title, abs, col 1 at lines 10-16), which are understood to be usable in medical therapy applications and to desirably exhibit an improved “functional half-life”, which leads to “desirable properties of prolonged clearance from the blood while retaining significant functional activity” (see, e.g., US’131 at col. 3 at lines 10-30).
NCBI NP_000564.124 is cited herein to establish that other human CR1 sequences were known in the prior art, which shares 1350/1351 residues with instant SEQ ID NOs: 3 and 21, except with respect to the Histidine tag of SEQ ID NO: 21 (compare instant NP000564 with instant SEQ ID NOs: 3 and SEQ ID NO: 1 at positions 42-1392).
US 9295713 B2 discloses methods of treating subjects by administering an sCR1 polypeptide comprising LHR A, B and C, without LHR D (see, e.g., US’713 at claims 1-2).
US 9649357 B2 discloses methods of treating subjects by administering an sCR1 polypeptide comprising LHR A, B and C, without LHR D (see, e.g., US’357 at claims 1-2).
US 9649356 B2 discloses methods of treating subjects by administering an sCR1 polypeptide comprising LHR A, B and C, without LHR D (see, e.g., US’356 at claims 1-4).
US 20160184392 A1 discloses methods of treating subjects by administering an sCR1 polypeptide comprising LHR A, B and C, without LHR D (see, e.g., US’392 at claims 1-2). US Application 17/618,076 is related, but directed to a presently unclaimed, unexamined invention (i.e., conjugates and methods thereof).
Conclusion
No claims are allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached at (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/RANDALL L BEANE/ Primary Examiner, Art Unit 1654
1 Examiner notes that claims 31-32 depend upon a canceled claim, but remain withdrawn for reasons of record.
2 Examiner notes that claims 36-37 depend upon a canceled claim, but remain withdrawn for reasons of record.
3 Cited in previous action.
4 Cited in previous action.
5 Cited in previous action.
6 Cohen et al., Journal of Visualized Experiments, v. 125:e56012, 11 pages, (July 2017); hereafter “Cohen”; cited in previous action
7 US2012/0232020 issued as US9649,356 on May 16, 2017, and the issued patent recites essentially identical claims.
8 NCBI NP_000564.2, complement receptor 1 isoform F precursor [Homo sapiens], ncbi.nlm.gov, NP_000564.2, 6 pages (Apr. 16, 2017), also available at https://www.ncbi.nlm.nih.gov/protein/NP_000564.2 (last visited 8/18/2025); hereafter “NP000564.2”.
9 Note that US’020 directs artisans to embodiments “of human CR1 comprising at least long homologous repeats (LHRs) B and/or C, preferably both LHRs B and C, more preferably long homologous repeats A, B, and C”.
10 See, e.g., US’020 at claims 1-5, ¶¶[0032], [0034],[0046]; see also discussions above.
11 See, e.g., US’020 at claims 1-5, ¶¶[0032], [0034],[0046]; see also discussions above.
12 See, e.g., Sirota et al., Single-residue posttranslational modification sites at the N-terminus, C-terminus or in-between: To be or not to be exposed for enzyme access. Proteomics. 2015 Jul;15(14):2525-46. doi: 10.1002/pmic.201400633. PMID: 26038108; PMCID: PMC4745020; hereafter “Sirota”; at title, abs, 2525 at § 1, 2525 to 2526 at bridging ¶, explaining that post-translational modifications are “Covalent chemical alterations of a proteins primary structure”, that “greatly influence protein size, hydrophobicity, charge and other physico-chemical properties and, therefore, change/enhance/inhibit specific protein activities or target the protein to another subcellular localization… ”.
13 See, e.g., Gupta et al., Production of Recombinant Pharmaceutical Proteins. Basic and Applied Aspects of Biotechnology. 2016 Oct 23:77–101. doi: 10.1007/978-981-10-0875-7_4. PMCID: PMC7120688; hereafter “Gupta”; at 82 at col II at “6”, noting that for selecting recombinant expression systems “Lack of posttranslational modifications (PTMs) is the problem, which cannot be solved, and is mandatory for activity of many therapeutic proteins…. PTMs play an important roll in proper protein folding, processing, stability, tissue targeting, activity, immune reactivity, and half-life of the protein. Lack of these results in insoluble, unstable, or inactive product”.
14 See, e.g., Chen et al., PTMap--a sequence alignment software for unrestricted, accurate, and full-spectrum identification of post-translational modification sites. Proc Natl Acad Sci U S A. 2009 Jan 20;106(3):761-6. doi: 10.1073/pnas.0811739106. Epub 2009 Jan 9. PMID: 19136633; PMCID: PMC2630079; hereafter “Chen”; at title, abs, Fig. 1 on 763.
15 See, e.g., Chen et al., PTMap--a sequence alignment software for unrestricted, accurate, and full-spectrum identification of post-translational modification sites. Proc Natl Acad Sci U S A. 2009 Jan 20;106(3):761-6. doi: 10.1073/pnas.0811739106. Epub 2009 Jan 9. PMID: 19136633; PMCID: PMC2630079; hereafter “Chen”; at title, abs, Fig. 1 on 763, 761 at col I at 1st full ¶ starting with “Mass”.
16 See, e.g., Sirota et al., Single-residue posttranslational modification sites at the N-terminus, C-terminus or in-between: To be or not to be exposed for enzyme access. Proteomics. 2015 Jul;15(14):2525-46. doi: 10.1002/pmic.201400633. PMID: 26038108; PMCID: PMC4745020; hereafter “Sirota”; at title, abs, 2525 at § 1, 2525 to 2526 at bridging ¶, explaining that post-translational modifications are “Covalent chemical alterations of a proteins primary structure”, that “greatly influence protein size, hydrophobicity, charge and other physico-chemical properties and, therefore, change/enhance/inhibit specific protein activities or target the protein to another subcellular localization… ”.
17 See, e.g., Gupta et al., Production of Recombinant Pharmaceutical Proteins. Basic and Applied Aspects of Biotechnology. 2016 Oct 23:77–101. doi: 10.1007/978-981-10-0875-7_4. PMCID: PMC7120688; hereafter “Gupta”; at 82 at col II at “6”, noting that for selecting recombinant expression systems “Lack of posttranslational modifications (PTMs) is the problem, which cannot be solved, and is mandatory for activity of many therapeutic proteins…. PTMs play an important roll in proper protein folding, processing, stability, tissue targeting, activity, immune reactivity, and half-life of the protein. Lack of these results in insoluble, unstable, or inactive product”.
18 See, e.g., Chen et al., PTMap--a sequence alignment software for unrestricted, accurate, and full-spectrum identification of post-translational modification sites. Proc Natl Acad Sci U S A. 2009 Jan 20;106(3):761-6. doi: 10.1073/pnas.0811739106. Epub 2009 Jan 9. PMID: 19136633; PMCID: PMC2630079; hereafter “Chen”; at title, abs, Fig. 1 on 763, 761 at col I at 1st full ¶ starting with “Mass”.
19 See, e.g., Sirota et al., Single-residue posttranslational modification sites at the N-terminus, C-terminus or in-between: To be or not to be exposed for enzyme access. Proteomics. 2015 Jul;15(14):2525-46. doi: 10.1002/pmic.201400633. PMID: 26038108; PMCID: PMC4745020; hereafter “Sirota”; at title, abs, 2525 at § 1, 2525 to 2526 at bridging ¶, explaining that post-translational modifications are “Covalent chemical alterations of a proteins primary structure”, that “greatly influence protein size, hydrophobicity, charge and other physico-chemical properties and, therefore, change/enhance/inhibit specific protein activities or target the protein to another subcellular localization… ”.
20 See, e.g., Gupta et al., Production of Recombinant Pharmaceutical Proteins. Basic and Applied Aspects of Biotechnology. 2016 Oct 23:77–101. doi: 10.1007/978-981-10-0875-7_4. PMCID: PMC7120688; hereafter “Gupta”; at 82 at col II at “6”, noting that for selecting recombinant expression systems “Lack of posttranslational modifications (PTMs) is the problem, which cannot be solved, and is mandatory for activity of many therapeutic proteins…. PTMs play an important roll in proper protein folding, processing, stability, tissue targeting, activity, immune reactivity, and half-life of the protein. Lack of these results in insoluble, unstable, or inactive product”.
21 That is, in addition to US’020, the pertinent prior art of record includes the following: US 9295713 B2 discloses methods of treating subjects by administering an sCR1 polypeptide comprising LHR A, B and C, without LHR D (see, e.g., US’713 at claims 1-2). US 9649357 B2 discloses methods of treating subjects by administering an sCR1 polypeptide comprising LHR A, B and C, without LHR D (see, e.g., US’357 at claims 1-2). US 9649356 B2 discloses methods of treating subjects by administering an sCR1 polypeptide comprising LHR A, B and C, without LHR D (see, e.g., US’356 at claims 1-4). US 20160184392 A1 discloses methods of treating subjects by administering an sCR1 polypeptide comprising LHR A, B and C, without LHR D (see, e.g., US’392 at claims 1-2).
22 That is, in addition to US’020, the pertinent prior art of record includes the following: US 9295713 B2 discloses methods of treating subjects by administering an sCR1 polypeptide comprising LHR A, B and C, without LHR D (see, e.g., US’713 at claims 1-2). US 9649357 B2 discloses methods of treating subjects by administering an sCR1 polypeptide comprising LHR A, B and C, without LHR D (see, e.g., US’357 at claims 1-2). US 9649356 B2 discloses methods of treating subjects by administering an sCR1 polypeptide comprising LHR A, B and C, without LHR D (see, e.g., US’356 at claims 1-4). US 20160184392 A1 discloses methods of treating subjects by administering an sCR1 polypeptide comprising LHR A, B and C, without LHR D (see, e.g., US’392 at claims 1-2).
23 Terpe, Overview of tag protein fusions: from molecular and biochemical fundamentals to commercial systems, Appl. Microbiol. Biotechnol., vol. 60:523-533 (2003); hereafter “Terpe”; cited in previous action.
24 NCBI NP_000564.1, complement component (3b/4b) receptor 1 isoform F precursor [Homo sapiens], ncbi.nlm.gov, NP_000564.1, 6 pages (Oct. 16, 2005), also available at https://www.ncbi.nlm.nih.gov/protein/NP_000564.1 (last visited 2/16/2023); cited in previous action; hereafter “NP000564”.